摘要：
目的:研究治疗便血方剂的用药规律及其“核心配伍-作用靶点”的关联性。方法:从《中医方剂大辞典》中筛选治疗便血的方剂，录入数据库，进行频数、聚类和关联分析，从中发现配伍组方规律。找到核心配伍组合后，再使用中药分子机制的生物信息学分析工具（Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, BATMAN-TCM）对核心配伍组合进行活性成分-靶点预测，从而分析核心配伍组合的共同作用靶点。结果:共收录便血方剂616首，涉及中药340味；排名前10的高频药物依次是当归、甘草、黄连、芍药、枳壳、生地黄、黄芩、地榆、槐花、黄芪；主要使用的中药类别依次是补虚药、清热药、止血药。发现生地黄、黄芩、赤芍，人参、白术、茯苓，侧柏叶、地榆、槐花，当归和川芎等是治疗便血的四组核心配伍组合；经分析发现这四组核心配伍组合均有AR、ESR1、NR3C1、PGR、VDR这5个共同作用靶点，即治疗便血的11个核心药物有5个共同作用靶点。结论:《中医方剂大辞典》所载便血方剂的核心配伍组合关联的AR、NR3C1、PGR、VDR等靶点与肠炎、结直肠癌、胃癌等常导致便血的相关疾病密切相关，提示其“核心配伍-作用靶点”的关联性对于指导临床用药以及相关基础研究和新药开发有一定参考意义。
期刊：
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS,2023年37(3):1381-1391 ISSN：0393-974X
通讯作者：
Chen, XY;Cai, HZ
作者机构：
[Deng, Xu; Chen, Xinyu; Xu, Zelin] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Prevent & Treatment Ctr, Changsha 410007, Hunan, Peoples R China.;[Luo, Yuntao] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Hlth Management, Changsha 410007, Hunan, Peoples R China.;[Cai, Huzhi] Hunan Univ Tradit Chinese Med, Hosp 1, Dept Int Med, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Chen, XY ; Cai, HZ ] H;Hunan Univ Tradit Chinese Med, Hosp 1, Dept Prevent & Treatment Ctr, Changsha 410007, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Hosp 1, Dept Int Med, Changsha 410007, Hunan, Peoples R China.
关键词：
Notch signal pathway;miR-18a-5p;chronic heart failure;cardiac function;cardiomyocyte;apoptosis
摘要：
Objectives: To explore how the mechanism of miR-18a-5p overexpression through the Notch signaling pathway improves cardiac function and inhibits cardiomyocyte apoptosis in chronic heart failure rats. Methods: Forty rats were randomly divided into contrast group, negative control (NC) group, high-expression group, and low -expression group by random number table, with ten rats in each group. NC group rats, high-expression group rats, and low -expression group rats were injected intraperitoneally with 2 mg/mL adriamycin solution to establish the rat model of chronic heart failure. The miR-18a-5p overexpression and inhibition lentivirus vector was constructed, and the miR-18a-5p overexpression and inhibition lentivirus suspension were injected into the myocardium of rats in the high-expression group and low-expression group respectively. No treatment was made in the contrast group and NC group. The expression levels of miR-18a-5p were detected in the myocardial tissue of rats and the cardiac function of rats. In addition, the apoptosis of rat cardiomyocytes was observed, and the expression levels of apoptosis-related proteins (Cleaved-caspase-3, Bax, and Bcl-2) were detected in the myocardial tissue of rats. The possible binding sites of miR-18a-5p and Notch2 3 ' untranslated region (UTR) region were predicted, and the interaction between miR-18a-5p and Notch2 was verified. Finally, the expression levels of Notch signal pathway-related genes and proteins (Notch2, Hes1, and Hes5) were detected in the myocardial tissue of rats. Results: In comparison with the NC group, miR-18a-5p expression levels in myocardial tissue of high-expression group rats increased (p < 0.05), and that of low-expression group rats decreased (p < 0.05). In contrast with the NC group and low-expression group, the values of left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD) in the high-expression group decreased (p < 0.05), and the values of left ventricular ejection fraction (LVEF) and fraction shortening (FS) of the left ventricle in the high-expression group increased (p < 0.05). In comparison with the NC group and low-expression group, myocardial cell apoptosis in the high-expression group decreased (p < 0.05), and the protein expression levels of Cleaved-caspase-3 and Bax in myocardial tissue of high-expression group rats decreased (p < 0.05). Moreover, the Bcl-2 protein expression levels in the myocardial tissue of high-expression group rats increased (p < 0.05). Through prediction and verification, miR-18a-5p might bind to the "GCACCUUA" site of the Notch2 3 ' UTR region, which could inhibit the activity of wild-type Notch2 3 ' UTR luciferase reporter plasmid but could not inhibit the activity of mutant Notch2 3 ' UTR luciferase reporter plasmid. In comparison with the NC group and low-expression group, the messenger ribonucleic acid (mRNA) and protein expression levels of Notch signal pathway-related factors Notch2, Hes1, and Hes5 in myocardial tissue of high-expression group rats were decreased (p < 0.05).Conclusions: miR-18a-5p overexpression could improve cardiac function and inhibit cardiomyocyte apoptosis in chronic heart failure rats, which might be related to the regulation of the Notch signal pathway.
期刊：
Cellular and Molecular Biology,2023年69(4):94-100 ISSN：0145-5680
通讯作者：
Chen, XY
作者机构：
[Chen, Qingyang; Dai, Feiyue; Lin, Quancheng] First Hosp Hunan Univ Chinese Med, Cent Intens Care Unit, Changsha, Hunan, Peoples R China.;[Liu, Jian] First Hosp Hunan Univ Chinese Med, Med Innovat Expt Ctr, Changsha, Hunan, Peoples R China.;[Li, Yan] First Hosp Hunan Univ Chinese Med, Vasc Tumor Intervent Dept, Changsha, Hunan, Peoples R China.;[Chen, Xinyu] First Hosp Hunan Univ Chinese Med, Internal Med Cardiovasc Dept, Changsha, Hunan, Peoples R China.
通讯机构：
[Chen, XY ] F;First Hosp Hunan Univ Chinese Med, Internal Med Cardiovasc Dept, Changsha, Hunan, Peoples R China.
关键词：
Bone marrow mesenchymal stem;cells;acute myocardial infarction;miR-183-5P;FOXO1;myocardial;ischemia
摘要：
The homing rate of transplanted mesenchymal stem cells (BMSCs) after acute myocardial infarction (AMI) is generally low, with only 0%-6% of the number of transplanted stem cells distributed to the heart; therefore, this study will investigate the therapeutic effects and mechanisms of miR-183-5p-modified BMSCs cells on myocardial ischemia and hypoxia caused by AMI. In this experiment, After first establishing the BMSCs ischemic-hypoxic injury model, the rats were divided into healthy group, model group, BMSCs group and BMSCs+ miR-183-5P group, where the healthy group was taken to normal culture, the model group caused myocardial ischemic-hypoxic damage, the BMSCs group underwent BMSCs stem cell transplantation on the basis of the model group, and the BMSCs+ miR-183-5P group was group was cultured with BMSCs-derived miR-183-5P on the basis of the model group. Myocardial tissue sections of rats in each group were taken for HE staining and histopathological changes were observed by light microscopy. The proliferation, apoptosis and migration ability of the cells were detected by CCK-8 method, flow cytometry and Transwell transfer method. The target gene of miR-183-5P was predicted using bioinformatics software, and the binding of miR-183-5P to FOXO1 was investigated. The expression of FOXO1 was analysed using qRT-PCR and protein blotting techniques. The qRT-PCR results showed that the expression of miR-183-5P was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The value-added ability and the migration capacity of BMSCs in the BMSCs group and BMSCs+ miR-183-5P group were increased compared with the model group, and the BMSCs+ miR-183-5P group BMSCs had the highest proliferation capacity and the migration capacity(P<0.05). In contrast, the apoptotic capacity of BMSCs was significantly reduced in the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the apoptotic capacity of BMSCs was lowest in the BMSCs+ miR-183-5P group (P<0.05). The bioinformatics software RegRNA 2. 0 was used to predict that the specific target gene that may be regulated by miR-183-5P is FOXO1 and confirmed that miR-183-5P does indeed have a targeting relationship with the FOXO1 pathway. After upregulation of miR-183-5P expression, the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The Western blotting showed that the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, especially the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). In conclusion, BMSCs-derived miR-183-5P can tar-get and regulate FOXO1 to increase the proliferation and migration of BMSCs and reduce their apoptosis, and can also reduce myocardial tissue edema and inflammatory response by increasing the expression of FOXO1 mRNA, which can increase the survival rate of BMSCs and provide a clinical basis for BMSCs transplantation.
摘要：
目的:探究不同中医证型的高血压病患者眼底体征的差异.方法:选取符合标准的患有高血压病的患者进行研究.通过中医辨证进行分组,利用改进的U-Net网络对患者眼底图片进行预处理及血管分割,通过imageJ软件KaPPa插件计算视网膜血管曲度,angle tool插件测量动静脉分支夹角,使用半自动化视网膜微血管测量软件VAM-PIRE(Vascular Asesment and Measuremnt Platform for Images of the Rtina)测量视网膜动静脉管径.对比分析视网膜微血管形态学指标在不同中医证型高血压病患者之间的差异.结果:共纳入相关临床资料、实验室指标、眼底照相检查完整的患者363例,通过对高血压病患者眼底图像分析发现肝火亢盛证患者视网膜病变分级多以Ⅲ级为主,而痰湿壅盛证和阴阳两虚证均以Ⅱ-Ⅲ级为主,阴虚阳亢组则以Ⅰ级为主.各组间颞上静脉、颞上动脉存在差异,其中痰湿壅盛组颞上静脉明显细于其他三组(P<0.05),肝火亢盛组颞上动脉粗于痰湿壅盛组(P<0.05)和阴虚阳亢组(P<0.05),但与阴阳两虚组无明显差异(P>0.05).颞下动静脉各组间差异无统计学意义(P>0.05).各证型间仅颞上静脉的血管分支夹角存在差异(P≤0.05),而其余视网膜血管组间无明显差异(P>0.05).各证型间静脉的血管弯曲情况无明显差异(P>0.05),视网膜动脉的血管弯曲情况存在明显差异(P<0.05).结论:不同中医证型的高血压性视网膜病变严重程度和视网膜血管形态学上存在差异,一定程度上反映中医辨证对高血压病进行中医分型的合理性,提供了眼底体征作为中医辨证分型的依据.提示或可通过高血压病的中医证型预测视网膜血管病变程度,进而预测靶器官的损伤程度.
