芪参颗粒对血管紧张素Ⅱ诱导的大鼠心肌成纤维细胞基质代谢的影响  

Effects of Qishen Granules on Matrix Metabolism of Rat Cardiac Fibroblasts Induced by Angiotensin Ⅱ

作　　者：谭桂兰 彭婧嫔 刘国维 钟李璐 袁敏 TAN Guilan;PENG Jingping;LIU Guowei;ZHONG Lilu;YUAN Min(People's Hospital of New District Longhua Shenzhen,Shenzhen 518000,China)

机构地区：[1]深圳市龙华区人民医院中医科,深圳518000

出　　处：《世界中医药》2022年第15期2167-2170,2177,共5页World Chinese Medicine

基　　金：国家自然科学基金地区科学基金项目(81760743)——绿原酸通过c-di-GMP信号通路调控铜绿假单胞菌生物被膜感染的作用及机制研究。

摘　　要：目的:通过观察芪参颗粒对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞(CFs)外基质(ECM)代谢的影响,探讨其抗心肌纤维化(MF)的分子机制。方法:将传代培养的乳鼠原代CFs细胞分为空白对照组、AngⅡ组、卡托普利组和芪参颗粒组。干预48 h后,检测CFs基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、Ⅰ型胶原蛋白(Col Ⅰ)、Ⅲ型胶原蛋白(Col Ⅲ)、基质金属蛋白酶组织抑制因子1(TIMP-1)、基质金属蛋白酶组织抑制因子-2(TIMP-2)的分泌情况及MMP-2、MMP-9、Col Ⅰ、Col Ⅲ、TIMP-1和TIMP-2 mRNA的表达情况。结果:CFs的增殖对比,AngⅡ组高于空白对照组,卡托普利组和芪参颗粒组低于AngⅡ组(P<0.01);Col Ⅰ、Col Ⅲ含量及其mRNA表达水平比较,AngⅡ组较空白对照组增加,卡托普利组与芪参颗粒组较AngⅡ组减少(P<0.01);MMP-2、MMP-9、TIMP-1和TIMP-2表达对比及MMP-2/TIMP2和MMP-9/TIMP-1比值对比,AngⅡ组较空白对照组前者显著增加,卡托普利组和芪参颗粒组较AngⅡ组均下降(P>0.05),芪参颗粒组较卡托普利组前者显著下降(P<0.01)。结论:芪参颗粒可抑制AngⅡ诱导的CFs的增殖,并减少CFs Col Ⅰ、Col Ⅲ的表达,效果优于卡托普利,其作用机制可能与下调MMP-2、MMP-9、TIMP-1、TIMP-2的表达,并降低MMP-2/TIMP-2、MMP-9/TIMP-1的比值,调控基质代谢有关。Objective:To observe the effects of Qichen Granules(QG) on the extracellular matrix(ECM) metabolism of cardiac fibroblasts(CFs) induced by Angiotensin Ⅱ(Ang Ⅱ),and explore the molecular mechanism of QG against myocardial fibrosis(MF).Methods:The passage cultured primary CFs were divided into a blank control group, an Ang Ⅱ group, a captopril group, and a QG group.After intervention for 48 h, the secretions and mRNA expression levels of matrix metalloproteinase(MMP)-2,MMP-9,type I collagen(Col Ⅰ),type Ⅲ collagen(Col Ⅲ),tissue inhibitor of metalloproteinase(TIMP)-1,and TIMP-2 were determined.Results:The Ang Ⅱ group had a higher proliferation of CFs than the blank control group, and the captopril group and the QG group had a lower proliferation of CFs than the Ang Ⅱ group(P<0.01).The content and mRNA expression levels of Col Ⅰ and Col Ⅲ were increased in the Ang Ⅱ group as compared with the blank control group but decreased in the captopril group and the QG group as compared with the Ang Ⅱ group(P<0.01).The expressions of MMP-2,MMP-9,TIMP-1,and TIMP-2 and the ratios of MMP2/TIMP2 and MMP9/TIMP1 were increased in the Ang Ⅱ group as compared with the blank control group, decreased in the captopril group and the QG group as compared with the Ang Ⅱ group(P>0.05),and were lower in the GQ group as compared with the captopril group(P<0.01).Conclusion:QG can inhibit the proliferation of Ang Ⅱ-induced CFs and reduce the expressions of Col Ⅰ and Col Ⅲ,which has a better effect than captopril.The mechanism may be related to the down-regulation of the expressions of MMP-2,MMP-9,TIMP-1,and TIMP-2,the reduction of the ratios of MMP-2/TIMP-2 and MMP-9/TIMP-1,and the regulation of matrix metabolism.

关 键 词：芪参颗粒 心肌纤维化 心肌成纤维细胞 细胞外基质 金属基质蛋白酶 基质金属蛋白酶组织抑制剂 卡托普利 血管紧张素Ⅱ 

分 类 号：R289.5[医药卫生—方剂学]