摘要
目的:结合网络药理学和传统中医理论构建治疗高血压心肌纤维化的新型中药复方——降压抗纤方,并探讨其对自发性高血压大鼠(SHR)心肌纤维化的治疗效果。方法:获取中药网络药理学数据库中药系统药理学数据库和分析平台(TCMSP)中的中药、成分和靶标等信息,运用网络分析软件Cytoscape从中筛选出能作用于高血压心肌纤维化疾病靶标的中药,再根据中医辨证理论和组方原则进一步筛选并构建复方。通过SHR动物模型实验观察降压抗纤方抗心机纤维化的作用,以5只正常血压大鼠(normal blood pressure rat,WKY)为空白组,30只12周龄的SHR大鼠随机分为5组,分别为高血压模型组(SHR),降压抗纤方低剂量组(KXL,2 g·kg^(-1)),降压抗纤方中剂量组(KXM,4 g·kg^(-1)),降压抗纤方高剂量组(KXH,8 g·kg^(-1))和卡托普利阳性药组(CAP,13.5 mg·kg^(-1)),每组5只。连续灌胃12周后停药,取材前禁食12 h。运用大鼠无创尾压仪和彩色多普勒超声诊断仪检测血压及心脏功能,运用组织学染色和相应检测试剂盒观察心脏组织形态学改变及血清生化指标。结果:确认降压抗纤方组成成分为丹参、三七、黄芪、鸡血藤和化橘红。动物实验结果表明,与正常组比较,模型组的血压明显升高(P〈0.01),心脏功能指标下降(P〈0.01),同时血清中心肌酶谱的水平升高(P〈0.05,P〈0.01),炎症因子水平升高(P〈0.05,P〈0.01);与模型组比较,各给药组能有效逆转上述指标(P〈0.05,P〈0.01)。结论:运用网络药理学和传统中医理论所构建的新型复方降压抗纤方具有抗高血压心肌纤维化的作用,并对肝肾无毒副作用。
Objective: To develop new Chinese medicine compound Jiangya Kangxian decoction for the treatment of hypertensive myocardial fibrosis using network pharmacology and traditional Chinese medicine( TCM)theory,in order to explore its therapeutic effect on hypertensive myocardial fibrosis in spontaneously hypertensive rats( SHR). Method: Data of Chinese herbs,ingredients,targets and diseases was obtained from traditional Chinese medine systems pharmacology( TCMSP) databases. Chinese herbs that can act on targets of hypertension and myocardial fibrosis were selected using Cytoscape,and then further screened out according to TCM theory of syndrome differentiation,in order to into a new Chinese medicine compound on the basis of the principles of formula composition. Five rats with normal blood pressure( WKY) were taken as blank group; 30 12-week-old SHR rats were taken as the study object and randomly divided into five groups: spontaneous hypertensive rat group( SHR),low-dose Jiangya Kangxian decoction group( KXL,2 g·kg^(-1)),moderate-dose Jiangya Kangxian decoction group( KXM,4 g·kg^(-1)),high-dose Jiangya Kangxian decoction group( KXH,8 g·kg^(-1)) and captopril positive control group( CAP,13. 5 mg·kg^(-1)). The rats were orally administered with drugs for consecutively 20 weeks and then fasted for 12 h before being put to death. The noninvasive tail voltmeter and Color Doppler were used to detect blood pressure and cardiac function. Tissue staining and biochemical kit were used to observed heart histomorphology and serum biochemical indexes. Result: It was confirmed that Jiangya Kangxian decoction consists of Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Astragali Radix,Spatholobi Caulis and Citri Grandis Exocarpium. The results of animal experiments showed that,compared with the normal group,the blood pressure of the model group increased significantly( P〈0. 01),the cardiac function index decreased( P〈0. 01),the levels of serum myocardial enzymes increased( P〈0. 05,P〈0. 01),and the level of inflammatory factors was increased( P〈0. 05,P〈0. 01). Compared with the model group,each drug group could effectively reverse the above indicators( P〈0. 05,P〈0. 01). Conclusion: Jiangya Kangxian decoction constructed by network pharmacology and TCM theory has a therapeutic effect on hypertensive myocardial fibrosis in SHR,with no side effects on liver and kidney.
作者
陈凯
刘馨
管怡晴
庄宇鑫
党文振
吕琳
张国华
CHEN Kai;LIU Xin;GUAN Yi-qing;ZHUANG Yu-xin;DANG Wen-zhen;LYU Lin;ZHANG Guo-hua(Southern Medical University,Guangzhou 510515,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第20期115-122,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金面上项目(81373811,81072937)
关键词
网络药理学
中药复方
高血压
心肌纤维化
自发性高血压大鼠
network pharmacology
Chinese herbal compound
hypertension
myocardial fibrosis
spontaneous hypertensive rat