摘要：
目的通过体内外实验研究大叶千斤拔对慢性盆腔炎大鼠的抗炎作用及其抗炎机制。方法细胞实验方面,以脂多糖(LPS)诱导RAW264.7小鼠巨噬细胞建立体外炎症模型,研究大叶千斤拔对LPS诱导的巨噬细胞炎症因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和NO的影响,探究其对炎症调控相关蛋白诱导型一氧化氮合酶(iNOS)和IκBα的影响。动物实验方面,应用雌二醇建立大鼠假动情后采用金黄色葡萄球菌、大肠杆菌、解脲脲原体经阴道植入到宫腔内建立慢性盆腔炎模型。造模成功后,随机分为模型组、阳性药物组(妇炎康)、大叶千斤拔低(4.25 g · kg~(-1))、中(8.5 g · kg~(-1))、高(17 g ·kg~(-1))剂量组并连续灌胃给药21 d,正常组、假手术组、模型组灌胃生理盐水。末次给药后,大鼠眼眶静脉丛取血检测血清中IL-6和TNF-α,取大鼠子宫及其附件进行HE染色观察其子宫内膜和输卵管形态。结果细胞实验结果表明,大叶千斤拔能显著降低由LPS诱导的巨噬细胞炎症因子TNF-α、IL-6和自由基NO的释放水平;抑制炎症因子调控相关蛋白IκBα的降解、降低iNOS等炎症相关蛋白的表达。动物实验结果表明,大叶千斤拔能显著降低盆腔炎大鼠血清中的炎症因子TNF-α、IL-6,且能很好地改善盆腔炎大鼠子宫和输卵管的炎症病变,增加子宫内膜厚度、缓解输卵管堵塞和粘连。结论大叶千斤拔对慢性盆腔炎的抗炎作用机制可能与其抑制IκBα蛋白的降解从而降低TNF-α、IL-6等炎症因子的释放,同时通过降低iNOS的表达进而显著降低NO的产生相关。 <&wdkj&>OBJECTIVE To explore the anti-inflammatory effect and mechanism of Flemingia macrophylla Merr. on chronic pelvic inflammatory disease (CPID) rats through in vivo and in vitro experiment. METHODS LPS-stimulated mouse macrophages RAW264.7 in vitro were applied to observe the effects of Flemingia macrophylla Merr. on expressions of inflammatory factors (TNF-α, IL-6) and free radical (NO) and inflammation related proteins (IκBα, iNOS). In vivo, estradiol was used to get false estrum, and then the CPID rat model was established by the infection of the mixture of Staphylococcus aureus,Escherichia coli and Ureaplasma urealyticum via transvaginal implantation into the uterine cavity. After successful modeling, the rats were randomly divided into the model group, the positive drug group (Fuyankang),the low-dose group (4.25 g ·kg~(-1)), the medium-dose group (8.5 g ·kg~(-1)), and the high-dose group (17 g ·kg~(-1)), and were given continuously by gavage for 21 d. The normal group, sham operation group and mode group were given saline solution. After the final administration, rats' blood was collected from orbital venous plexus,and the serum levels of inflammatory cytokines IL-6 and TNF-a were measured by Elisa method. The rat's uterus and its accessories were studied by HE staining to observe the morphology of its endometrium and fallopian tubes. RESULTS Flemingia macrophylla Merr. can reduce the release levels of TNF-a,IL-6 and NO,inhibit the degradation of IκBα,and also reduce the expression of inducible nitric oxide synthase (iNOS) in RAW264.7 cells induced by LPS. Moreover, it can significantly improve the pathological state of the uterus and fallo pian tubes of rats with CPID, and reduce TNF-a and IL-6 in the serum of rats with CPID. CONCLUSION The anti-inflammatory effect mechanism of Flemingia macrophylla Merr. on CPID may be related to inhibiting the degradation of IκBα,thereby reducing the release of inflammatory factors such as TNF-a,IL-6, and significantly reducing the generation of NO by decreasing the expression of iNOS.
摘要：
Long noncoding RNA-steroid receptor RNA activator (LncRNA-SRA) is transcribed from a class of noncoding genes, and plays a critical role in regulating cell proliferation. However, the effect of lncRNA-SRA remains unclear in vascular proliferative diseases. In the present study, we overexpressed lncRNA-SRA in vitro, then investigated the biological consequences. A vascular damage mice model was constructed by performing femoral artery wire injury. LncRNA-SRA was overexpressed in the injured arteries, and significantly promoted the expression of ki67, thereby caused an overall increase in neointima formation. LncRNA-SRA overexpression led to the proliferation and migration of vascular smooth muscle cells (VSMCs). By stimulating the phosphorylation of MEK, ERK and CREB (cyclic nucleotide responsive element binding protein), lncRNA-SRA promoted VSMC proliferation. Meanwhile, these effects were blocked by the MEK inhibitor U0126. Therefore, lncRNA-SRA promoted VSMC proliferation by activating the MEK-ERK-CREB pathway. LncRNA-SRA could be a promising therapeutic target in vascular diseases characterized by neointimal hyperplasia.
摘要：
Type 2 diabetes mellitus (T2DM) is a chronic degenerative endocrine and metabolic disease with high mortality and morbidity, yet lacks effective therapeutics. We recently generated a novel fusion peptide INSR-IgG4Fc, Yiminsu (YMS), to facilitate the high-affinity binding and transportation of insulin. Thus, the aim of the present study was to determine whether the novel recombinant peptide, YMS, could contribute to restoring insulin sensitivity and glycaemic control in insulin resistance models and revealing its underlying mechanism. Palmitic acid (PA)-treated LO2 cells and high fat diet (HFD)-fed mice were treated with YMS. Therapeutic effects of YMS were measured using Western blotting, ELISA, qPCR, Histology and transmission electron microscopy. We observed that YMS treatment effectively improved insulin signaling in PA-treated LO2 cells and HFD-fed mice. Notably, YMS could significantly reduce serum levels of glucose, triglycerides, fatty acids and cholesterol without affecting the serum insulin levels. Moreover, our data demonstrated that YMS could restore glucose and lipid homeostasis via facilitating insulin transportation and reactivating PI3K/Akt signaling in both PA-treated cells and liver, gastrocnemius and brown fat of HFD-fed mice. Additionally, we noticed that the therapeutic effects of YMS was similar as rosiglitazone, a well-recognized insulin sensitizer. Our findings suggested that YMS is a potentially candidate for pharmacotherapy for metabolic disorders associated with insulin resistance, particularly in T2DM.
期刊：
Research Reviews in Pharmacology,2019年103(5-6):282-290 ISSN：0031-7012
通讯作者：
Qin, Li;Huang, Hong-Lin
作者机构：
[Shi, Ya-Ning; Zhang, Chan-Juan; Liao, Duan-Fang; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Shi, Ya-Ning; Zhang, Chan-Juan; Liao, Duan-Fang; Qin, Li] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.;[Huang, Hong-Lin; Zhang, Xiu-Qin] Univ South China, Dept Pharmacol, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Zhe-Yu] Cent S Univ, Hunan Canc Hosp, Changsha, Hunan, Peoples R China.;[Hu, Zhe-Yu] Cent S Univ, Affiliated Canc Hosp, Xiangya Med Sch, Changsha, Hunan, Peoples R China.
通讯机构：
[Qin, Li] H;[Huang, Hong-Lin] U;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;Univ South China, Dept Pharmacol, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Apoptosis;Cardiomyocytes;Genistein;Hypoxia
摘要：
BACKGROUND/AIMS: Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury. METHODS: Cobalt chloride (CoCl2) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1alpha and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis. RESULTS: In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1alpha was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl2-induced cell death and suppressed HIF-1alpha expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl2-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression. CONCLUSIONS: Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.
作者机构：
[林丽美; 刘月新; Lin, Yan; 吴萍; 肖榕; 廖端芳] Key Laboratory for Quality Evaluation of Bulk Herbs, College of Pharmacy, Hunan University of Chinese Medicine Changsha 410208, China;[林艳] College of Physics and Electronic, Central South University Changsha 410012, China;[李春] Key Laboratory for Quality Evaluation of Bulk Herbs, College of Pharmacy, Hunan University of Chinese Medicine Changsha 410208, China Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China
通讯机构：
Key Laboratory for Quality Evaluation of Bulk Herbs, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
作者机构：
[杜可] Department of Pharmacology, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[廖端芳] Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, China;[张婵娟; Qin L.; 石雅宁] Department of Pharmacology, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China, Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构：
[Qin, Li] D;Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha 410208, China.
摘要：
Angiopoietin-like protein 3 (ANGPTL3) belongs to a multifunctional secreted protein that mainly expresses in the liver, and is regulated by numerous post-translational modifications, including multiple cleavage and glycosylation. Accumulating evidences have revealed that ANGPTL3 plays a critical role in both biological processes, such as lipid metabolism, angiogenesis and haematopoietic function and pathological changes, including atherosclerosis, carcinogenesis, nephrotic syndrome, diabetes, liver diseases and so on. Thus, ANGPTL3 may serve as a potential biomarker in these diseases. Furthermore, ANGPTL3 signalling pathways including LXR/ANGPTL3, thyroid hormone/ANGPTL3, insulin/ANGPTL3 and leptin/ANGPTL3 are also involved in physiological and pathological processes. Some biological ANGPTL3 inhibitors, chemical drugs and traditional Chinese medicine exert beneficial effects by targeting ANGPTL3 directly or indirectly. Therefore, elucidating the effects and underlying mechanisms of ANGPTL3 is essential to develop promising strategies in the diagnosis and treatment of related diseases.
作者机构：
[夏伯候; 廖扬振; 庹勤慧] Hunan University of Chinese Medicine, Changsha, 410208, China;Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China;Institute of TCM Diagnostics, Changsha, 410208, China;Hunan Province Pharmacy “Twelve Five” Key Disciplines, Changsha, 410208, China;[陈光宇] Hunan University of Chinese Medicine, Changsha, 410208, China, Engineering Center of Medicinal and Edible Functional Food, Hunan University of Chinese Medicine, Changsha, 410208, China, Institute of TCM Diagnostics, Changsha, 410208, China
通讯机构：
[Liao, D.] H;Hunan University of Chinese MedicineChina
作者机构：
[Gu, Hong-Feng; Li, Na; Tang, Ya-Ling; OuYang, Xin-Ping] Univ South China, Dept Physiol, Hengyang, Peoples R China;[Gu, Hong-Feng; Li, Na; Tang, Ya-Ling; OuYang, Xin-Ping] Univ South China, Inst Neurosci, Hengyang, Peoples R China;[Yan, Can-Qun; Yi, Si-Ni; Zhou, Hao-Ling] Univ South China, Affiliated Hosp 2, Dept Endocrine, Hengyang, Peoples R China;[Shi, Zhe; Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China
通讯机构：
[OuYang, Xin-Ping] U;[Liao, Duan-Fang] H;Univ South China, Dept Physiol, Hengyang, Peoples R China. Univ South China, Inst Neurosci, Hengyang, Peoples R China. Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
关键词：
autophagy;cognitive function;diabetes mellitus;hippocampus;mammalian target of rapamycin complex;nicotinate-curcumin
摘要：
INTRODUCTION: Our previous study has confirmed that a novel curcumin derivate nicotinate-curcumin (NC) can facilitate autophagic flux in THP-1 cells induced by oxidized low-density lipoprotein. AIMS: Given that autophagy plays critical roles in neurodegenerative diseases, the present study was carried out to investigate whether NC can improve cognitive function of rats with diabetes mellitus (DM) via restoring autophagic flux in CA1 hippocampus. RESULTS: Our results showed that NC treatment improved cognitive deficit and attenuated neuronal loss as well as cellular ultrastructure impairment in the CA1 region of DM rats induced by streptozotocin. Moreover, NC lowered the expressions of the apoptosis-related proteins Bcl-2, Bax, Cyt-c, and cleaved Caspase-3. Notably, NC treatment reversed autophagic flux impairment as evidenced by the deceases in LC3-II and p62 protein levels, and autophagosome accumulation in the hippocampal CA1 region of DM rats. However, these protective effects of NC were abolished by cotreatment with 3-methyladenine (an autophagy inhibitor) and chloroquine (an autophagic flux inhibitor), respectively. Furthermore, NC treatment decreased the expressions of phosphorylated mammalian target of rapamycin (mTOR) and p70 ribosomal protein S6 kinase (p70S6k) proteins in the CA1 region of DM rats. CONCLUSIONS: These results indicate that NC ameliorates DM-induced cognitive function impairment via restoring autophagic flux might by inhibiting mTOR/p70S6k activation in the CA1 region, and NC may be a promising agent for diabetic cognitive dysfunction prevention and treatment.
