Abnormal Glu/mGluR2/3/PI3K pathway in the hippocampal neurovascular unit leads to diabetesrelated depression
作者:
Wang, Yu-Hong;Liu, Jian;Han, Yuan-Shan;Liu, Lin;Tang, Lin;...
期刊:
中国神经再生研究:英文版 ,2021年16(4):727-733 ISSN:1673-5374
通讯作者:
Wang, YH
作者机构:
[Han, Yuan-Shan; Wang, Yu-Hong; Tang, Lin; Liu, Jian; Liu, Lin] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Zhao, Hong-Qing; Yang, Hui] Hunan Univ Chinese Med, Inst Innovat & Appl Res, Changsha, Hunan, Peoples R China.;[Meng, Pan; Zhao, Hong-Qing; Yang, Hui] Hunan Univ Chinese Med, Key Lab Chinese Mat Med Power & Innovat Drugs Est, Changsha, Hunan, Peoples R China.;[Meng, Pan; Zhao, Hong-Qing; Yang, Hui] Hunan Univ Chinese Med, Domest First Class Construct Discipline Chinese M, Changsha, Hunan, Peoples R China.
通讯机构:
[Wang, YH ] H;Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.
关键词:
caspase 3;caspase 9;corticosterone;dexamethasone;excitatory amino acid transporter 1;glial cell line derived neurotrophic factor;glial fibrillary acidic protein;glucocorticoid receptor;glucose;glutamic acid;metabotropic receptor 2;metabotropic receptor 3;mitogen activated protein kinase;phosphatidylinositol 3 kinase;platelet endothelial cell adhesion molecule 1;vesicular glutamate transporter 3;animal experiment;animal model;Article;astrocyte;brain capillary endothelial cell;capillary endothelial cell;cell survival;cell viability;controlled study;depression;diabetes mellitus;down regulation;electric resistance;enzyme activity;enzyme linked immunosorbent assay;female;hippocampus;immunocytochemistry;neuroapoptosis;nonhuman;protein expression;rat;signal transduction;upregulation;Western blotting
摘要:
Our previous studies have shown that glutamate and hippocampal neuron apoptosis are key signals and direct factors associated with diabetes-related depression, and structural and functional damage to the hippocampal neurovascular unit has been associated with diabetes-related depression. However, the underlying mechanism remains unclear. We hypothesized that diabetes-related depression might be associated with the glutamate (Glu)/metabotropic glutamate receptor2/3 (mGluR2/3)/phosphoinositide 3-kinase (PI3K) pathway, activated by glucocorticoid receptors in the hippocampal neurovascular unit. To test this hypothesis, rat hippocampal neurovascular unit models, containing hippocampal neurons, astrocytes, and brain microvascular endothelial cells, were treated with 150 mM glucose and 200 μM corticosterone, to induce diabetes-related depression. Our results showed that under conditions of diabetes complicated by depression, hippocampal neurovascular units were damaged, leading to decreased barrier function; elevated Glu levels; upregulated glucocorticoid receptor, vesicular glutamate transporter 3 (VGLUT-3), and metabotropic glutamate receptor 2/3 (mGluR2/3) expression; downregulated excitatory amino acid transporter 1 (EAAT-1) expression; and alteration of the balance of key proteins associated with the extracellular signal-regulated kinase (ERK)/glial cell-derived neurotrophic factor (GDNF)/PI3K signaling pathway. Moreover, the viability of neurons was dramatically reduced in the model of diabetes-related depression, and neuronal apoptosis, and caspase-3 and caspase-9 expression levels, were increased. Our results suggest that the Glu/mGluR2/3/PI3K pathway, induced by glucocorticoid receptor activation in the hippocampal neurovascular unit, may be associated with diabetes-related depression. This study was approved by the Laboratory Animal Ethics Committee of The First Hospital of Hunan University of Chinese Medicine, China (approval No. HN-ZYFY-2019-11-12) on November 12, 2019. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.
语种:
英文
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百合地黄汤对焦虑性抑郁症模型大鼠海马突触可塑性的影响
作者:
赵洪庆;刘检;孟盼;杨蕙;蔺晓源;...
期刊:
中国中药杂志 ,2021年46(05):1205-1210 ISSN:1001-5302
作者机构:
[赵洪庆; 孟盼; 余曦明; 王宇红] 湖南中医药大学科技创新中心/中药粉体与创新药物国家重点实验室培育基地;[刘检; 龙红萍; 蔺晓源; 杨蕙] 湖南中医药大学第一附属医院中心实验室
关键词:
百合地黄汤;焦虑性抑郁症;海马;突触可塑性;树突棘;超微结构;结构与功能
摘要:
探讨百合地黄汤对焦虑性抑郁症模型大鼠海马神经元突触可塑性的影响。将50只SD大鼠随机分为正常组、模型组、文拉法辛组(6.75 mg·kg-1)、百合地黄汤高剂量组(8.64 g·kg-1)和百合地黄汤低剂量组(4.32 g·kg-1)。采用慢性束缚应激(6 h)联合皮质酮(ih, 30 mg·kg-1)的方法建立焦虑性抑郁症模型,于造模7 d后开始灌胃给药,共给药21 d。评价大鼠的焦虑和抑郁样行为,Golgi-Cox染色和电镜技术分别观察突触树突棘形态及超微结构变化,免疫荧光法检测海马突触结构蛋白突触素1(synapsin-1)和突触后致密蛋白95(postsynaptic densityprotein-95,PSD-95)的表达,Western blot法检测功能蛋白突触囊泡蛋白(synaptophysin, SYP)、认知缺陷突触相关蛋白(synaptic Ras GTPase activating protein, SynGap)的表达。结果显示,模型组大鼠焦虑抑郁样行为明显,海马树突棘密度及分枝长度均降低,突触数量减少,内部结构损伤明显,synapsin-1和PSD-95平均荧光强度显著降低,SYP和SynGap表达下降;高剂量百合地黄汤能显著改善模型大鼠的焦虑和抑郁样行为,缓解突触损伤,增加突触synapsin-1,PSD-95,SYP,SynGap蛋白的表达。因此,作者认为百合地黄汤能够通过调控海马神经元突触可塑性改善焦虑和抑郁行为。
语种:
中文
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GR/NF-κB signaling pathway regulates hippocampal inflammatory responses in diabetic rats with chronic unpredictable mild stress
作者:
Li, Zi-Rong;Han, Yuan-Shan;Liu, Zhuo;Zhao, Hong-Qing;Liu, Jian;...
期刊:
European Journal of Pharmacology ,2021年895(1):173861 ISSN:0014-2999
通讯作者:
Wang, YH;Liu, Z
作者机构:
[Wang, Yu-Hong; Zhao, Hong-Qing; Li, Zi-Rong] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.;[Han, Yuan-Shan; Liu, Jian; Yang, Hui] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Expt Ctr Med Innovat, Changsha, Hunan, Peoples R China.;[Liu, Zhuo] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Educ & Sci, Changsha 410012, Hunan, Peoples R China.
通讯机构:
[Liu, Z ; Wang, YH ] H;Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.;Hunan Acad Tradit Chinese Med, Affiliated Hosp, Dept Educ & Sci, Changsha 410012, Hunan, Peoples R China.
关键词:
Chronic unpredictable mild stress;Diabetic model rats;GR;Hippocampal;Inflammatory;NF-κB signaling pathway
摘要:
Clinical studies have shown that diabetes can present with underlying depression, and a combination of the two can lead to emotional, memory and cognitive disorders, closely associated with hippocampal neuroinflammation. However, the mechanism underlying the development of hippocampal neuroinflammation under the above condition remains elusive. The aims of this study were to explore the pathogenesis of diabetes combined with depression, and the effect of dexamethasone (Dex), a glucocorticoid receptor (GR) agonist, on hippocampal neuroinflammation in diabetic rats with chronic unpredictable mild stress (CUMS). Therefore, rats were intra-gastrically fed on a high-fat diet (10% cholesterol 10 ml/kg) for 14 days and thereafter injected with 38 mg/kg of streptozotocin on the 15th day to induce diabetes. Dex treatment of the diabetic and CUMS rats ameliorated the depression-associated behavior in the respective rats. Apart from enhanced depressive behavior, diabetes-depressed condition also up-regulated the expression of hippocampus micmglia chemokine I receptor (CX3CR1) and secretion of several pro-inflammatory factors, in particular, interleukin 1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor - alpha (TNF-alpha). Hematoxylin-eosin staining revealed inflammatory damages in the hippocampus. Western blot analysis further revealed repression of GR proteins converse to the nuclear factor kappa-B (NF-kappa B) proteins, which were up-regulated. Intriguingly, Dex reversed the above events by inhibiting inflammatory reactions in the hippocampus. Consequently, played an antidepressant effect in diabetic and CUMS model rats. Overall, findings of this research suggest that the physiopathology of diabetes with stress cormobity are mediated by inflammatory reactions in the hippocampus. In particular, the responses are associated with regulation of GR/NF-kappa B signaling pathway.
语种:
英文
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复方柴金解郁片对慢性应激抑郁大鼠HPA轴及炎症因子的影响
作者:
王宇红;张尚霞;马明玥;赵洪庆;孟盼;...
期刊:
中国新药杂志 ,2020年29(5):514-519 ISSN:1003-3734
作者机构:
[王宇红; 赵洪庆; 孟盼; 马明玥; 李姿蓉; 韩远山; 张尚霞; 吴梦瑶] Hunan University of Traditional Chinese Medicine, National Key Laboratory Breeding Base of Chinese Medicine Powders and Innovative Drugs/Technology Innovation Center, Changsha, 410208, China
关键词:
复方柴金解郁片;抑郁症;下丘脑-垂体-肾上腺轴;炎症因子
摘要:
目的:研究复方柴金解郁片对慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴( HPA轴)及炎症因子的影响。方法:连续慢性应激建立抑郁大鼠模型,用开野和水迷宫实验检测大鼠行为学变化,ELISA法检测大鼠血浆中促肾上腺皮质激素释放激素( corticosteroid-releasing hormone,CRH) 、促肾上腺皮质激素( adrenocorticotropic hormone,ACTH) 、皮质酮( corticosterone,CORT)及血清中白介素8( interleukin-8,IL-8) 、白介素18( interleukin 18,IL-18) 、白介素10( interleukin 10,IL-10)的含量。结果:在抑郁大鼠模型中,复方柴金解郁片高剂量组( 2.7 g·kg ~(-1) )明显降低CRH,ACTH,CORT,IL-8,IL-18含量,显著升高IL-10含量。结论:复方柴金解郁片具有显著的抗抑郁效果,其抗抑郁机制可能与改善HPA轴及炎症因子水平有关。
语种:
中文
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The correlation between adiponectin and FGF9 in depression disorder.
作者:
Wang, Xiao-Qing;Li, Wei-Hui;Tang, Ya-Hui;Wu, Li-Feng;Zeng, Gui-Rong;...
期刊:
Brain Research ,2020年1729:146596 ISSN:0006-8993
通讯作者:
Cheng, Ze-Neng;Jiang, DJ
作者机构:
[Cheng, Ze-Neng; Wang, Xiao-Qing] Cent South Univ, XiangYa Pharm Sch, Changsha 410083, Peoples R China.;[Tang, Ya-Hui; Jiang, De-Jian; Wu, Li-Feng; Zeng, Gui-Rong; Cheng, ZN; Wang, Xiao-Qing] Hunan Ctr Safety Evaluat & Res Drugs, Changsha 410013, Peoples R China.;[Tang, Ya-Hui; Jiang, De-Jian; Wu, Li-Feng; Zeng, Gui-Rong; Cheng, ZN; Wang, Xiao-Qing] Hunan Key Lab Pharmacodynam & Safety Evaluat New, Changsha 410013, Peoples R China.;[Li, Wei-Hui] Cent South Univ, XiangYa Hosp 2, Dept Psychiat, Changsha 410011, Peoples R China.;[Wang, Yu-Hong; Jiang, De-Jian] Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Changsha 410208, Peoples R China.
通讯机构:
[Jiang, DJ ; Cheng, ZN] H;Hunan Ctr Safety Evaluat & Res Drugs, Changsha 410013, Peoples R China.;Hunan Key Lab Pharmacodynam & Safety Evaluat New, Changsha 410013, Peoples R China.
关键词:
Adiponectin (ADPN);Depression;Fibroblast growth factor 9 (FGF9);Fibroblast growth factor receptor 3 (FGFR3)
摘要:
Adiponectin (ADPN) and fibroblast growth factor 9 (FGF9) has been reported as anti-depressive and pro-depressive factor, respectively. However, it is unknown whether there is directly interaction between ADPN and FGF9 in depression. The present study aims to investigate the correlation between ADPN and FGF9 in depression disorder. Firstly, the decreased level of ADPN and the increased level of FGF9 in plasma of depressive patients compared with non-depressive subjects were observed. Furthermore, these is a significant negative correlation between the ratio of ADPN to FGF9 and the total score of Hamilton Depression Scale in total investigated subjects. The similar changes of ADPN and FGF9 were also observed in elder adiponectin gene knockout (Adipo−/−) mice with an increasing trend to depressive-like behaviors. Secondly, the decreasing level of ADPN and increasing level of FGF9 in plasma and hippocampus tissues were observed in chronic unpredictable mild stress (CUMS)-induced depression in ICR mice with significant depressive-like behaviors and hippocampus damage, which attenuated by injection of recombinant ADPN or FGF9 antibody into lateral ventricle. In Adipo−/− mice, injection of FGF9 antibody into lateral ventricle also attenuated CUMS-induced depressivelike behaviors. The protein expression of FGF receptor 3 (FGFR3), the main receptor of FGF9, was significantly down-regulated in hippocampus tissues of CUMS-treated mice, which could be attenuated by treatment with either recombinant ADPN or anti-FGF9. In summary, the present results suggest that ADPN maybe a key negative regulator of FGF9/FGFR3 in depressive disorder and the dysfunction of ADPN-FGF9 pathway plays a key role in stress-induced depression. © 2019 Elsevier B.V.
语种:
英文
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复方柴金解郁片通过改善海马神经元突触功能发挥抗抑郁作用(英文)
作者:
李姿蓉;韩远山;吴梦瑶;刘检;金狮;...
期刊:
数字中医药(英文) ,2020年(02):80-95 ISSN:2096-479X
作者机构:
1. 湖南省中药粉体与创新药物省部共建国家重点实验室培育基地;2. 湖南中医药大学第一附属医院;3. 千金药业股份有限公司;4. 湖南省脑科医院
关键词:
复方柴金解郁片;抑郁症;突触可塑性;认知
摘要:
目的探讨复方柴金解郁片(CJJYT)对抑郁症认知障碍的改善作用及其潜在机制。方法体外实验中,从胎鼠全脑中分离海马,进一步培养海马神经元细胞;实验前18 h,除对照组外,每组均加50μM CORT构建抑郁环境;建立模型后,空白血清组加10%空白血清,CJJYT组、文拉法辛组分别加入对应10%含药血清,空白组和模型组则加入等体积培养液。检测各组海马神经元细胞内Ca2+平均荧光强度;记录m EPSC电流幅度和频率,评估海马神经元的突触功能。此外,通过免疫荧光染色,高内涵分析海马神经元突触可塑性相关蛋白SYN-α、NR2A、NR2B、PSD-95、Ca MKⅡ和Syn GAP的表达;采用反转录聚合酶链反应检测SYN-α、 NR2A、 NR2B、PSD-95、Ca MKⅡ和Syn GAP的m RNA表达。在体内实验中,除对照组外,其他大鼠均孤笼饲养,并采用慢性不可预知性应激刺激复制抑郁模型,并给予相应的药物干预。通过行为学测试评估抑郁大鼠的学习、记忆能力及其他认知能力;采用酶联免疫吸附测定法检测各组大鼠CORT水平;采用Golgi-Cox染色观察海马CA1和DG神经元突触形态的变化。结果体外实验:CJJYT干预降低了海马神经元细胞内Ca2+平均荧光强度(P <0.05),并降低m EPSC的频率和电流幅度(P <0.05),从而抑制了突触后受体的过度活动。CJJYT干预降低了海马神经元SYN-α,NR2A,NR2B和PSD-95的蛋白表达和m RNA表达(P <0.05);增加Ca MKⅡ和Syn GAP蛋白表达和m RNA的表达(P <0.05),从而改善海马神经元的突触可塑性。在体内,CJJYT干预可改善蔗糖偏爱,自主活动,Morris水迷宫测试的学习和记忆能力(P <0.05),抑制食欲和增加强迫游泳测试绝望感(P <0.05);CJJYT干预可降低CORT水平(P <0.05),促进海马神经元突触损伤的修复。结论 CJJYT可以改善大鼠海马的突触功能,对海马神经元有显著的保护作用,可修复海马神经元的结构损伤,提高抑郁模型大鼠的认知能力,其改善认知的机制可能与SYN-α/NR及其下游神经递质的传递和功能有关。
语种:
中文
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复方七芍降压片对SHR大鼠P2Y6、MEK1/2、ERK1/2及血管重塑标志物MMP-9、TIMP-1蛋白表达的影响
作者:
任卫琼;李弘;刘叶倩;龚姗;刘林;...
期刊:
中药新药与临床药理 ,2020年31(02):156-162 ISSN:1003-9783
作者机构:
湖南中医药大学,湖南 长沙410208;湖南中医药大学第一附属医院,湖南 长沙 410007;[曾勇; 张稳; 刘林; 刘叶倩; 李弘; 龚姗] 中医药大学第一附属医院;[任卫琼; 王宇红] 湖南中医药大学
关键词:
复方七芍降压片;高血压;血管重塑;炎症
摘要:
目的研究复方七芍降压片对自发性高血压大鼠(SHR)肠系膜动脉中G蛋白偶联受体P2Y6、酪氨酸激酶受体(MEK1/2)、丝裂原活化蛋白激酶(ERK1/2)及血管重塑标志物基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制剂-1(TIMP-1)等蛋白表达的影响,探讨复方七芍降压片干预血管重塑的作用机制。方法将雄性SHR大鼠随机分为模型组、厄贝沙坦片组(13.5 mg·kg~(-1))、复方七芍降压片组(8.73 g·kg~(-1)),每组10只,另设10只WKY大鼠为正常对照组;灌胃给药,每日1次,连续给药6周。采用无创血压仪测定每周大鼠尾动脉血压;ELISA法检测大鼠血清中白细胞介素-1β(IL-1β)水平;免疫组化法检测肠系膜动脉中P2Y6、MEK1/2、ERKl/2、MMP-9及TIMP-1蛋白的表达;肠系膜动脉组织HE染色后进行体视学分析,测量肠系膜动脉血管中膜厚度及相同位置的管腔直径,计算两者比值作为动脉壁厚度(WT)值。结果与正常对照组比较,模型组大鼠各周血压明显上升(P <0.01);肠系膜动脉P2Y6、MEKl/2、ERKl/2、MMP-9蛋白表达及MMP-9/TIMP-1比值、WT值明显升高(P<0.05,P<0.01), TIMP-1表达明显降低(P<0.01);血清中IL-1β水平明显升高(P<0.01)。药物干预后,与模型组比较,复方七芍降压片组各周血压均明显降低(P<0.01);肠系膜动脉P2Y6、MEKl/2、ERKl/2、MMP-9蛋白表达及MMP-9/TIMP-1比值、WT值均明显降低(P < 0.05,P<0.01),TIMP-1表达明显升高(P<0.05);血清中IL-1β水平明显降低(P <0.05)。结论复方七芍降压片能够显著降低SHR大鼠血压,改善血管重塑,可能与调控肠系膜动脉中P2Y6、MEKl/2、ERK1/2蛋白表达,减轻炎症反应有关。
语种:
中文
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复方七芍降压片对TNF-α诱导的与平滑肌细胞共培养的血管内皮细胞P2Y6信号通路相关因子表达的影响
作者:
刘叶倩;李弘;龚姗;陈春茗;马丹凤;...
期刊:
中国中医药信息杂志 ,2020年27(11):58-65 ISSN:1005-5304
作者机构:
湖南中医药大学第一附属医院;[马丹凤] 湖南省儿童医院;湖南中医药大学药学院;湖南中医药大学科技创新中心;[曾勇; 刘林; 陈春茗; 任卫琼; 李弘; 刘叶倩; 龚姗] 湖南中医药大学附属第一医院
关键词:
复方七芍降压片;内皮细胞;平滑肌细胞;炎症反应;血管重塑;大鼠
摘要:
目的 观察复方七芍降压片对肿瘤坏死因子-α(TNF-α)诱导的与平滑肌细胞共培养的血管内皮细胞中炎症因子与P2Y6、MEK1/2、ERK1/2蛋白表达的影响,探讨其治疗高血压的机制.方法 采用内皮细胞和平滑肌细胞构建共培养体系,利用炎症因子TNF-α 建立高血压炎症微环境.将共培养好的细胞随机分为正常组、模型组、空白血清组、MRS2578组、厄贝沙坦药物血清组、复方七芍药物血清组、MRS2578+复方七芍药物血清组.MRS2578组和MRS2578+复方七芍药物血清组加入10μmol/L MRS2578.正常组和模型组加入等量培养液,余各组加入10%药物血清及空白血清.采用倒置显微镜观察内皮细胞和平滑肌细胞形态;采用ELISA检测细胞上清液炎症因子白细胞介素(IL)-1β、IL-10水平;采用免疫荧光、Western blot、RT-qPCR技术检测内皮细胞P2Y6、MEK1/2、ERK1/2的表达.结果 与正常组比较,模型组和空白血清组内皮细胞和平滑肌细胞数量明显减少,细胞轮廓不清晰,折光性降低,漂浮的死细胞团块增多;IL-1β含量显著增加,IL-10含量显著减少(P<0.01);P2Y6、MEK1/2、ERK1/2荧光强度、灰度值、mRNA水平明显升高(P<0.01).与模型组比较,复方七芍药物血清组内皮细胞和平滑肌细胞折光性增强,细胞形态恢复正常;IL-1β水平明显降低(P<0.05);P2Y6、MEK1/2、ERK1/2荧光强度、灰度值、mRNA水平明显降低(P<0.01).结论 复方七芍降压片可明显调控TNF-α诱导的内皮炎症反应,改善内皮炎症导致的平滑肌细胞损伤,维持其正常功能,其机制可能与调控内皮细胞P2Y6受体及其下游信号通路MEK1/2、ERK1/2蛋白表达,改善炎症反应有关.
语种:
中文
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抑郁症“脑郁”病机探讨及应用
作者:
蔺晓源;孟盼;龙红萍;韩远山;胡国恒;...
期刊:
中国中医药信息杂志 ,2020年27(3):10-13 ISSN:1005-5304
作者机构:
湖南中医药大学第一附属医院,湖南长沙 410007;湖南中医药大学中医学国内一流建设学科,湖南长沙 410208;湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地,湖南长沙 410208;[胡国恒; 韩远山; 蔺晓源; 龙红萍] 中医药大学第一附属医院;[王宇红; 孟盼] 湖南中医药大学
关键词:
抑郁症;肝郁气滞;脑失神明;肝脑相关;脑郁
摘要:
抑郁症属中医学“郁证”范畴,病始在肝,与脑相关。本文基于抑郁症“肝郁气滞”基本病机和“脑失神明”的病机关键,立足“肝脑相关”,提出“脑郁”病机理论,并通过对原发性抑郁症、糖尿病并发抑郁症、乳腺癌并发抑郁症、卒中后抑郁和焦虑性抑郁症中医病机特点及治法方药的系统性研究,体现抑郁症“脑郁”病机理论的合理性,为抑郁症辨证论治提供新的思路。
语种:
中文
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复方柴金解郁片治疗肝郁脾虚型抑郁症的临床观察
作者:
卓丹;贺海霞;李姿蓉;于静波;赵洪庆;...
期刊:
中医药导报 ,2020年26(16):72-77 ISSN:1672-951X
作者机构:
湖南中医药大学,湖南长沙410208;湖南中医药大学第一附属医院,湖南长沙410007;湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,湖南长沙410208;[赵洪庆; 于静波; 李姿蓉; 卓丹; 王宇红] 湖南中医药大学;[贺海霞; 姚欣艳; 蔺晓源] 中医药大学第一附属医院
关键词:
抑郁症;肝郁脾虚型;复方柴金解郁片;盐酸舍曲林;汉密尔顿抑郁量表;匹兹堡睡眠质量指数量表
摘要:
目的:观察复方柴金解郁片治疗肝郁脾虚型抑郁症的临床疗效及安全性。方法:采用随机、对照原则,将80例肝郁脾虚型抑郁症患者按照随机数字表法分为治疗组和对照组各40例。治疗组予复方柴金解郁片治疗,对照组予盐酸舍曲林治疗。分别于治疗前和治疗后第4周、第8周对两组汉密尔顿抑郁量表(HAMD-17)、匹兹堡睡眠质量指数量表(PSQI)、中医证候积分、中医证候疗效、疾病疗效及睡眠效率进行记录对比。结果:在治疗中,两组患者HAMD-17评分、PSQI评分及中医证候评分均从第4周开始出现下降趋势,直至第8周结束。睡眠效率从第4周开始得到改善,直至第8周结束,两组组内治疗前后比较,差异均有统计学意义(P<0.05)。治疗组与对照组疾病疗效评价总有效率分别为86.49%(32/37)、84.21%(32/38),两组比较,差异无统计学意义(P>0.05),但治疗组治疗后第4周、第8周中医证候疗效总有效率均显著高于对照组,且在治疗8周后差异均有统计学意义(P<0.05)。两组不良反应发生率比较,治疗组低于对照组,差异有统计学意义(P<0.05)。结论:复方柴金解郁片治疗肝郁脾虚型抑郁症疗效肯定,与西药盐酸舍曲林疗效相当,能够显著改善患者的抑郁行为和睡眠质量,提高患者生活质量,不良反应少,安全性较高。
语种:
中文
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左归降糖解郁方对糖尿病并发抑郁症大鼠下丘脑IRS - 1/PI3K/AKT信号通路的影响
作者:
杨蕙;黄会珍;金狮;刘检;蔺晓源;...
期刊:
时珍国医国药 ,2020年31(05):1076-1079 ISSN:1008-0805
作者机构:
湖南中医药大学第一附属医院, 湖南, 长沙, 410007;湖南中医药大学, 湖南省中药粉体与创新药物省部共建国家重点实验室培育基地, 湖南, 长沙, 410007;[刘检; 杨蕙; 韩远山; 蔺晓源] 中医药大学第一附属医院;[文诗仪; 王宇红; 黄会珍; 金狮] 湖南中医药大学
关键词:
糖尿病并发抑郁症;左归降糖解郁方;下丘脑;胰岛素受体;胰岛素受体底物-1
摘要:
目的研究左归降糖解郁方对糖尿病并发抑郁症大鼠下丘脑IRS-1/PI3K/AKT信号通路的影响。方法将糖尿病并发抑郁症模型动物随机分为模型组、阳性药组(二甲双胍0.18g/kg +氟西汀1.8mg/kg)、左归降糖解郁方高剂量组(20.53g/kg)和低剂量组(10.26g/kg),每组8只。另取8只健康大鼠为正常组。灌胃给药28d并每周测量动物体重。实验结束后,采用血糖仪检测大鼠空腹血糖。采用免疫荧光法检测大鼠下丘脑p -IR,p - IRS - 1、p -PI3K,p - Akt蛋白的表达。结果与正常组比较,模型组大鼠体重显著降低而血糖含量显著升高(P <0.01),下丘脑p - IR,p - IRS -1,p -PI3K,p-Akt蛋白表达水平均显著降低(P<0.01)。与模型组比较,在体重方面,左归降糖解郁方高剂量组大鼠体重在给药的第2周至第4周有显著性增加(P<0.01),而低剂量组大鼠体重仅第3周和第4周有显著性差异;在血糖方面,左归降糖解郁方的2个剂量均可显著降低大鼠的血糖(P<0.01);在胰岛素信号方面,左归降糖解郁方高剂量组可显著升高模型大鼠下丘脑p - IR,p - IRS -1,p - PI3K,p - Akt的表达,而低剂量仅对p - IR和p - IRS -1蛋白的表达有显著性影响(P<0.01或P<0.05)。结论左归降糖解郁方可有效改善糖尿病并发抑郁症大鼠下丘脑的胰岛素信号通路,从而改善动物脑内的胰岛素抵抗状态。
语种:
中文
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一种多功能的实验动物行为学检测和造模装置
发明/设计人:
刘林 ;王宇红 ;姜帆 ;杨蕙 ;刘检 ;...
申请/专利权人:
湖南中医药大学第一附属医院((中医临床研究所))
申请/专利号:
CN202020375314.0
申请时间:
2020-03-23
公开号:
CN211931939U
公开时间:
2020-11-17
摘要:
一种多功能的实验动物行为学检测和造模装置,包括实验箱、调节支架和摄像装置;实验箱包括含有底板且上方敞口的箱体、分隔板和隔离笼;分隔板包括相互垂直的板材,分隔板可拆卸的匹配设在箱体内将箱体分隔成多个格子;箱体底板设有恒温加热装置,箱体侧壁上设有能调节恒温加热装置温度的控制面板;调节支架的下端设在箱体上,调节支架的顶端设有摄像装置,调节支架上至少包含一个旋转铰接机构和至少一个升降调节机构使得摄像装置的位置可以调整。本实用新型不仅能够分别完成旷场实验、扭体实验、热板实验及社会交互行为实验,而且还可以用于精神类等疾病的动物模型应激造模。具有经济实用、功能多、准度高、使用范围广的特点和优势。
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百事乐胶囊对皮质酮暴露大鼠海马神经元神经营养相关蛋白表达的影响
作者:
王华;凌佳;赵洪庆;蔺晓源;王宇红;...
期刊:
中国中医药信息杂志 ,2020年27(7):48-53 ISSN:1005-5304
作者机构:
湖南中医药大学第一附属医院, 湖南, 长沙, 410007;湖南中医药大学科技创新中心, 湖南, 长沙, 410208;中药粉体与创新药物湖南省省部共建国家重点实验室培育基地, 中药粉体与创新药物湖南省省部共建国家重点实验室培育基地, 湖南, 长沙, 410208;[赵洪庆; 凌佳; 王宇红; 孟盼] 湖南中医药大学;[蔺晓源; 王华] 湖南中医药大学附属第一医院
关键词:
百事乐胶囊;抑郁症;海马神经元;血清和糖皮质激素诱导激酶1;神经营养
摘要:
目的观察百事乐胶囊药物血清对皮质酮暴露大鼠原代海马神经元神经营养相关蛋白表达的影响,探讨其治疗抑郁症的潜在机制。方法采用受孕18 d的SD大鼠胎鼠进行海马神经元原代培养,将神经元随机分为正常组、空白血清组、皮质酮暴露组、氟西汀药物血清组、百事乐胶囊药物血清组。除正常组外,其余各组给予相应干预的同时进行高浓度皮质酮暴露。干预18 h后,光学显微镜下观察神经元生长情况,MTT法检测海马神经元细胞活力,高内涵分析技术检测神经营养相关蛋白的表达。结果与正常组比较,皮质酮暴露组神经元存活率显著降低(P<0.01),树突断裂或明显减少,神经网络连接减少,脑源性神经营养因子(BDNF)、神经营养因子-3(NT-3)及神经生长因子(NGF)蛋白表达显著降低(P<0.05,P<0.01),血清和糖皮质激素诱导激酶1(SGK1)蛋白表达明显升高(P<0.01);与皮质酮暴露组比较,氟西汀药物血清组和百事乐胶囊药物血清组神经元存活率明显升高(P<0.05),胞间网络更丰富,BDNF、NT-3及NGF蛋白表达显著升高(P<0.05,P<0.01),SGK1蛋白表达显著降低(P<0.05)。结论百事乐胶囊可提高皮质酮暴露下海马神经元细胞活力,促进神经细胞可塑性,并可通过SGK1信号增强神经营养。
语种:
中文
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芍药苷对氯化钴诱导PC12细胞氧化应激损伤的保护作用
作者:
雷昌;黄丹;向韵;张秀丽;孟盼;...
期刊:
中成药 ,2020年42(10):2605-2610 ISSN:1001-1528
作者机构:
[张秀丽; 向韵; 黄丹; 雷昌; 王宇红; 邹蔓姝; 凌成利; 孟盼] 湖南中医药大学;湖南中医药大学科技创新中心
关键词:
芍药苷;脑卒中;氧化应激;凋亡
摘要:
目的研究芍药苷对氯化钴诱导PC12细胞氧化应激损伤的保护作用。方法芍药苷预先处理PC12细胞1 h,再加入CoCl_2共孵育24 h。采用MTT法检测PC12细胞存活率,利用DCFH-DA探针、Annexin FITC-V/PI双染法、JC- 1探针检测芍药苷(100、200 μg /mL)对PC12细胞ROS水平、细胞凋亡率及线粒体膜电位值(MMP)的影响。结果CoCl_2诱导PC12细胞24 h后,其半数抑制浓度(IC_(50) )为1.2 mmol /L。与模型组比较,200 μg /mL芍药苷提高CoCl_2诱导PC12细胞存活率(P<0.05),减少细胞内ROS水平(P< 0.05),抑制细胞凋亡(P< 0.05),提高MMP(P<0.05) 。结论芍药苷对CoCl_2诱导PC12细胞氧化应激损伤有显著保护作用。
语种:
中文
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左归降糖解郁方对糖尿病并发抑郁症大鼠海马胰岛素抵抗的影响
作者:
杨蕙;刘检;唐林;蔺晓源;罗薇絮;...
期刊:
中草药 ,2020年51(11):3013-3020 ISSN:0253-2670
通讯作者:
Wang, Y.-H.
作者机构:
[刘检; 韩远山; 刘林; 蔺晓源; 唐林; 杨蕙] First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, 410007, China;[罗薇絮; 孟盼; 王宇红] Key Laboratory of Chinese Materia Medica Power and Innovation Drugs Established by Provincial and Ministry, Hunan University of Chinese Medicine, Changsha, 410007, China
通讯机构:
[Wang, Y.-H.] K;Key Laboratory of Chinese Materia Medica Power and Innovation Drugs Established by Provincial and Ministry, China
关键词:
左归降糖解郁方;糖尿病并发抑郁症;海马;胰岛素抵抗;胰岛素受体(IR);胰岛素受体底物-1(IRS-1);磷脂酰肌醇3-激酶(PI3K);蛋白激酶B(Akt)
摘要:
目的 研究左归降糖解郁方对糖尿病并发抑郁症大鼠海马胰岛素抵抗的调节作用.方法 建立糖尿病并发抑郁症大鼠模型,并随机分为4组,模型组,阳性药组(二甲双胍0.18 g/kg+氟西汀1.8 mg/kg),左归降糖解郁方高、低剂量组(20.52、10.26g/kg),另设健康大鼠为对照组.各组大鼠ig给药28 d后,采用血糖仪及ELISA法检测空腹血糖及外周胰岛素抵抗程度.采用旷野实验和强迫游泳实验检测大鼠抑郁样行为.采用免疫荧光法和Western blotting法检测大鼠海马胰岛素受体磷酸化蛋白(p-IR)、磷酸化的胰岛素受体底物-1 (p-IRS-1)的表达,采用Western blotting法检测海马磷酸化的磷脂酰肌醇3-激酶(p-PI3K)、磷酸化蛋白激酶B (p-Akt)蛋白的表达.结果 与对照组比较,模型组大鼠血糖显著升高并伴随明显的外周胰岛素抵抗,其在旷野实验中的活动次数显著降低、在强迫游泳实验中的不动时间显著延长;蛋白检测结果表明大鼠脑内p-IR、p-IRS-1、p-PI3K、p-Akt表达水平均显著降低.与模型组比较,左归降糖解郁方高剂量组大鼠血糖水平显著降低,外周胰岛素抵抗水平减轻,其在旷野实验中的活动次数显著增加、在强迫游泳实验中的不动时间显著缩短,而海马内p-IR、p-IRS-1、p-PI3K、p-Akt表达显著升高.结论 左归降糖解郁方可有效调节糖尿病并发抑郁症大鼠海马胰岛素信号通路,从而改善动物脑内的胰岛素抵抗状态.
语种:
中文
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左归降糖解郁方对糖尿病并发抑郁症大鼠海马神经血管单元联动损伤的调控作用及其机制
作者:
刘检;刘林;杨蕙;韩远山;王宇红
期刊:
北京中医药大学学报 ,2020年43(11):918-926 ISSN:1006-2157
作者机构:
湖南中医药大学第一附属医院 湖南 410007;[王宇红] 湖南省中药粉体与创新药物省部共建国家重点实验室培育基地;湖南中医药大学科技创新中心;[刘检; 杨蕙; 刘林; 韩远山] 中医药大学第一附属医院
关键词:
左归降糖解郁方;糖尿病并发抑郁症;神经血管单元;联动损伤;凋亡;大鼠
摘要:
目的 探讨左归降糖解郁方对糖尿病并发抑郁症(DD)大鼠海马神经血管单元(NVU)联动损伤的调控作用及其潜在机制.方法 原代分离、纯化和培养SD大鼠海马神经元(Ne)、星形胶质细胞(As)与脑微血管内皮细胞(Bm),并对其进行免疫荧光染色鉴定;采用高糖联合皮质酮及Transwell小室干预构建DD海马NVU细胞模型;实验设正常组、模型组、空白血清组、左归降糖解郁方含药血清组.造模及给药18 h后,检测海马NVU跨内皮细胞电阻值(TEER)及4 h渗漏试验液面高度值;采用ELISA法分别检测Bm分泌蛋白白血病抑制因子(LIF)及As分泌蛋白转化生长因子 β(TGF-β)、胶质细胞源性神经营养因子(GDNF)含量;采用免疫荧光联合高内涵细胞成像(HCA)分别检测Bm结构蛋白的闭合蛋白-1(claudin-1)、紧密连接蛋白(occludin)及As结构蛋白的胶质纤维酸性蛋白(GFAP)、缝隙连接蛋白-43(CX43)表达水平;采用CCK-8法检测NVU中海马神经元细胞活力;采用Tunel染色法检测NVU中海马神经元细胞凋亡情况.结果 与正常组比较,模型组及空白血清组TEER值明显降低、4 h渗漏试验液面高度值明显升高,Bm分泌蛋白LIF及As分泌蛋白TGF-β、GDNF含量明显降低,Bm结构蛋白claudin-1、occludin及As结构蛋白GFAP、CX43表达下调,海马神经元细胞存活率下降,同时细胞凋亡明显增多;与模型组比较,左归降糖解郁方含药血清组TEER值显著增加、4 h渗漏试验液面高度值明显下降,分泌蛋白LIF、TGF-β、GDNF及结构蛋白claudin-1、occludin、GFAP、CX43表达显著上调,同时海马神经元细胞存活率增加,细胞凋亡显著减少.结论 左归降糖解郁方对DD大鼠海马NVU联动损伤具有明显的调控作用,其作用机制与改善海马NVU屏障功能、分泌功能及基础结构有关.
语种:
中文
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基于AKT/mTOR信号通路探讨复方七芍降压片治疗自发性高血压大鼠的作用机制
作者:
李弘;刘叶倩;龚姗;刘林;曾勇;...
期刊:
北京中医药大学学报 ,2020年43(04):296-303 ISSN:1006-2157
作者机构:
湖南中医药大学第一附属医院, 湖南, 410007;湖南中医药大学, 科技创新中心;[曾勇; 刘林; 任卫琼; 刘叶倩; 李弘; 龚姗; 蔡晓] 中医药大学第一附属医院;[王宇红] 湖南中医药大学
关键词:
调控蛋白激酶/雷帕霉素靶蛋白信号通路;自噬;炎症反应;复方七芍降压片;自发性高血压大鼠
摘要:
目的探讨复方七芍降压片通过调控蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路对自发性高血压(SHR)大鼠血压、炎症因子及胸主动脉自噬相关蛋白表达的影响。方法SHR大鼠30只,随机分为模型组、厄贝沙坦片组(27 mg/kg)、复方七芍降压片组(1.73 g/kg),连续给药6周,另设10只WKY大鼠为正常组,灌胃生理盐水。分别在给药前及给药1、2、3、4、5、6周,测量各组大鼠尾动脉血压。给药6周后取材,电镜观察胸主动脉超微结构及自噬情况;ELISA法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平;免疫组化法检测胸主动脉中Beclin-1、Bcl-2、 AKT、mTOR蛋白表达;Western-blot检测胸主动脉中Beclin-1、Bcl-2蛋白表达。结果与正常组比较,模型组大鼠血清IL-1β、IL-6水平升高(P <0.01);胸主动脉Bcl-2、AKT、mTOR蛋白表达升高(P <0.01或P <0.05),Beclin-1表达降低(P <0.01),且未见明显的自噬体结构。与模型组比较,复方七芍降压片组大鼠各周血压均降低(P <0.01);血清IL-1β、IL-6水平降低(P <0.05);胸主动脉中AKT、mTOR蛋白表达均降低(P <0.05),Beclin-1表达升高(P <0.05),且可见明显的自噬体结构。结论复方七芍降压片能够降低SHR大鼠血压,其机制可能与抑制胸主动脉中自噬相关信号通路蛋白AKT、mTOR的表达,促进主动脉自噬,改善炎症反应有关。
语种:
中文
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复方七芍降压片对SHR大鼠IL-8、IL-10水平及AP-1、MCP-1蛋白表达的影响
作者:
任卫琼;李弘;刘叶倩;龚姗;刘林;...
期刊:
中成药 ,2020年42(4):1031-1034 ISSN:1001-1528
作者机构:
湖南中医药大学第一附属医院;[王宇红] 湖南中医药大学;[刘林; 刘叶倩; 李弘; 任卫琼; 龚姗] 中医药大学第一附属医院
关键词:
复方七芍降压片;高血压;炎症因子
摘要:
目的研究复方七芍降压片对SHR大鼠肠系膜动脉组织AP-1、MCP-1蛋白表达及血清中IL-8、IL-10水平的影响。方法 30只雄性SPF级SHR大鼠随机分为模型组、厄贝沙坦片组(27 mg/kg)、复方七芍降压片组(8. 73 g/kg生药),另设10只WKY大鼠为正常对照组。无创血压仪测定尾动脉血压,透射电镜技术观察肠系膜动脉壁超微结构,ELISA法检测血清中IL-8、IL-10水平,免疫组化法检测肠系膜动脉中AP-1、MCP-1蛋白表达。结果与正常对照组比较,模型组大鼠各周大鼠血压均上升(P<0. 01),肠系膜动脉中AP-1、MCP-1蛋白表达升高(P<0. 01),血清中IL-8水平升高(P<0. 01)、IL-10水平降低(P<0. 01)。药物干预后与模型组比较,复方七芍降压片组各周血压均降低(P<0. 01),肠系膜动脉中AP-1、MCP-1蛋白表达降低(P<0. 05),血清中IL-8水平降低(P<0. 01)、IL-10水平升高(P<0. 01)。结论复方七芍降压片能够显著改善SHR大鼠血压,其机制可能与调控肠系膜动脉中AP-1、MCP-1蛋白表达,减轻炎症反应有关。
语种:
中文
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Compound Chai Jin Jie Yu Tablets, Acts as An Antidepressant by Promoting Synaptic Function in the Hippocampal Neurons
作者:
李姿蓉;韩远山;吴梦瑶;刘检;金狮;...
期刊:
数字中医药(英文) ,2020年3(2):80-95 ISSN:2096-479X
通讯作者:
Wang Yu-Hong
作者机构:
[Shi J.; Yu-Hong W.; Zi-Rong L.] State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Jian L.; Yuan-Shan H.] The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;[Meng-Yao W.] Qianjin Pharmaceutical Co., Ltd., Zhuzhou, Hunan 412000, China;[Xi Z.] Hunan Provincial Brain Hospital, Changsha, Hunan 410007, China
通讯机构:
[Wang Yu-Hong] S;State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
关键词:
SYN-α/NR
摘要:
Objective: To investigate the effectiveness of compound Chai Jin Jie Yu Tablets (CJJYT) in ameliorating cognitive impairment associated with depression and its potential mechanism of action. Methods: In vitro experiments, the hippocampus was isolated from the whole brain of the fetal rat and cultured into hippocampal neuron cells. 50 μM corticosterone (CORT) was added to each group 18 h before the experiment for modeling depression, with the exception of the control group. After modeling, the blank serum group was added with 10% blank serum, the CJJYT group and the venlafaxine group were added with the corresponding 10% drug-containing serum, and the control group and the model group were added with equal volumes of culture medium. The intracellular Ca2+ mean fluorescence intensity, miniature excitatory postsynaptic current (mEPSC) current amplitude, and frequency of different hippocampal neurons were evaluated as indicators of synaptic function in the hippocampal neurons. In addition, the expression of synaptic plasticity related proteins, synaptophysin-α (SYN-α), N-methyl-D-aspartate receptor 2A (NR2A), N-methyl-D- aspartate receptor 2B (NR2B), post synaptic density 95 protein (PSD-95), calcium/calmodulin dependent protein kinaseⅡ (CaMKⅡ) and synaptic associated protein (SynGAP) were detected in the hippocampal neurons by immunofluorescence staining and high content analysis (HCA) system. Then, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of SYN-α, NR2A, NR2B, PSD- 95, CaMKⅡ and SynGAP. For in vivo experiments, except for those in the blank control group, all rats were treated within a single cage for chronic unpredictable stress-induced depression modeling and subjected to corresponding drug interventions. Behavioral tests were used to detect depressive behavior and determine learning, memory and other cognitive abilities, whereas enzyme-linked immunosorbent assay (ELISA) was used to detect the CORT levels. Golgi-Cox staining was used to observe changes in the synaptic morphology of parahippocampal gyrus CA1 area (CA1) and dentategyrus (DG). Results: In vitro, CJJYT treatment reduced the intracellular Ca2+ mean flurorescence intensity in the hippocampal neurons (P < 0.05), causing a reduction in the frequency and current amplitude of mEPSC (P < 0.05), and thus inhibited the excessive activation of post-synaptic receptors. CJJYT treatment reduced the protein and mRNA expression of SYN-α, NR2A, NR2B and PSD-95 in the hippocampal neurons (P < 0.05), increased the mRNA and protein expression of CaMKⅡ and SynGAP (P < 0.05), and thereby improved the synaptic plasticity of the hippocampal neurons. In vivo, CJJYT intervention improved sucrose preference, voluntary activity, learning and memory ability of Morris water maze test, and suppressed appetite (P < 0.05), and increased the despair feeling of forced swimming test (P < 0.05). The CORT level was reduced (P < 0.05), leading to the repair of synaptic damage in the hippocampal neurons. Conclusions: CJJYT can improve the synaptic function of hippocampal neurons and has obvious protective effects on neurons. It can repair the structural damage in the hippocampal neurons, improving the cognitive ability of the depressed model rats. The mechanism of CJJYT improving cognition in depressed rats may be related to the transmission and function of SYN-α/NR and its downstream neurotransmitters. © 2020 Digital Chinese Medicine
语种:
英文
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Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury
作者:
Ling, Chengli;Lei, Chang;Zou, Manshu;Cai, Xiong;Xiang, Yun;...
期刊:
Journal of International Medical Research ,2020年48(9):030006052094585 ISSN:0300-0605
通讯作者:
Wang, YH
作者机构:
[Cai, Xiong; Ling, Chengli; Lei, Chang; Wang, Yuhong; Zou, Manshu; Xiang, Yun; Huang, Dan] Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Training Base Prov Minist Joint State Key Lab Chi, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Xie, Yu] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha, Hunan, Peoples R China.;[Li, Xuran] Hunan Univ Chinese Med, Sch Pharm, Changsha, Hunan, Peoples R China.
通讯机构:
[Wang, YH ] H;Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Training Base Prov Minist Joint State Key Lab Chi, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词:
apigenin;cobalt chloride;reactive oxygen metabolite;triphenyltetrazolium;apigenin;neuroprotective agent;adult;animal cell;animal experiment;animal model;animal tissue;apoptosis;Article;brain infarction;brain mitochondrion;cell activation;cell viability;cerebral ischemia reperfusion injury;controlled study;drug effect;drug mechanism;IC50;in vitro study;in vivo study;male;middle cerebral artery occlusion;mitochondrial membrane potential;neuroprotection;nonhuman;oxidative stress;PC12 cell line (pheochromocytoma);rat;animal;brain ischemia;cerebral artery disease;reperfusion injury;Animals;Apigenin;Apoptosis;Brain Ischemia;Infarction, Middle Cerebral Artery;Neuroprotective Agents;Oxidative Stress;Rats;Reperfusion Injury
摘要:
Objective: The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, both in vitro and in vivo. Methods: We first treated PC12 cells with cobalt chloride (CoCl2) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores. Results: The half-inhibitory concentration of CoCl2 was 1.2 mM. Pretreatment with 10 µg ⋅ mL−1 apigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl2-induced injury in vitro. In addition, apigenin treatment in vivo significantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation. Conclusions: Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injury in vitro and in vivo. © The Author(s) 2020.
语种:
英文
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