作　　者： ; (冼绍祥）; (王陵军）;

机构地区： 广州中医药大学

出　　处： 《中药新药与临床药理》 2022年第8期1083-1092,共10页

摘　　要： 目的基于转录组学和网络药理学探讨心阴片(黄芪、麦冬、毛冬青等)防治慢性心力衰竭(CHF)的作用机制。方法随机将32只雄性C57BL/6J小鼠分为假手术组、模型组、心阴片组(910 mg·kg^(-1))、培哚普利组(0.607 mg·kg^(-1)),每组8只。采用胸主动脉弓缩窄术(TAC)复制小鼠CHF模型。造模成功后,按照上述剂量灌胃给药(10 mL·kg^(-1)),每日1次,连续8周。采用心脏超声检测小鼠心功能,记录小鼠左室射血分数(LVEF)及左室短轴缩短率(LVFS)等指标;采用Masson染色法观察小鼠心脏组织病理形态变化,测定心肌纤维化面积;取小鼠心脏组织提取RNA进行转录组测序,并对组间差异基因进行GO功能及KEGG通路富集分析。通过TCMSP、TCMID平台结合文献补充筛选出心阴片的活性成分,利用SwissTargetPrediction网站预测活性成分作用靶点;通过GeneCards、OMIM数据库检索CHF疾病相关靶点;通过Venny 2.1平台对心阴片活性成分作用靶点与CHF疾病相关靶点取交集,并对交集靶点进行GO功能及KEGG通路富集分析;使用Venny平台对转录组的差异基因、网络药理的交集靶点取交集,获得心阴片治疗CHF的关键靶点;利用STRING平台构建关键靶点蛋白互作(PPI)网络;采用qPCR法检测关键靶点mRNA表达。结果与假手术组比较,模型组小鼠的LVEF、LVFS显著降低(P<0.01),心脏体积明显增大,心脏系数显著升高(P<0.01),心肌纤维化面积显著增加(P<0.01)。与模型组比较,给药组小鼠的LVEF、LVFS显著升高(P<0.01),心脏体积明显缩小,心脏系数显著降低(P<0.01),心肌纤维化面积显著减少(P<0.01)。共得到心阴片96个活性成分及其潜在作用靶点886个,CHF疾病相关靶点2345个,心阴片-CHF交集靶点285个;假手术组vs模型组共有3179个差异基因,模型组vs心阴片组共有822个差异基因,进一步取交集得到256个转录组差异基因;获得10个心阴片治疗CHF的关键靶点:CD38、CCND1、MMP8、CXCR3、GPR35、 Objective To investigate the mechanism of Xinyin Tablets in the prevention and treatment of chronic heart failure(CHF)based on transcriptomics and network pharmacology.Methods Thirty-two male C57BL/6J mice were randomly divided into the sham operation group,the model group,the Xinyin Tablets group(910 mg·kg^(-1)),and Perindopril group(0.607 mg·kg^(-1)),with 8 mice in each group.The mouse CHF model was replicated using transverse aortic constriction(TAC).After successful modelling,the mice were administered by gavage(10 mL·kg^(-1))at the above dose once daily for consecutive 8 weeks.The cardiac function of the mice was measured by cardiac ultrasound,and the left ventricular ejection fraction(LVEF)and left ventricular ejection fraction(LVFS)were recorded;the histomorphological changes of the mice were observed by Masson staining,and the area of myocardial fibrosis was measured;the RNA was sequenced and GO function and KEGG pathway enrichment analysis were performed for the genes that differed between groups.The active ingredients of Xinyin Tablets were screened by TCMSP and TCMID platforms with literature supplementation,and the targets of the active ingredients were predicted by SwissTargetPrediction website;the targets related to CHF disease were searched by GeneCards and OMIM database;the targets of the active ingredients of Xinyin Tablets were intersected with the targets related to CHF disease by Venny platform.The intersection of the active ingredient targets and CHF-related targets was performed on the Venny platform,and GO function and KEGG pathway enrichment analyses were performed on the intersection targets;the intersection of the transcriptomic differential genes and network pharmacology targets was performed on the Venny platform to obtain the key targets of CHF treatment with Xinyin Tablets;the key target protein-protein interaction(PPI)network was constructed on the STRING platform;the mRNA expression of key target was detected by qPCR.Results Compared with the sham operation group,LVEF and LVFS i

关 键 词： 心阴片 慢性心力衰竭 心功能 心肌纤维化 转录组学 网络药理学 小鼠

领　　域： [医药卫生—中药学] [医药卫生—中医学]