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
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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


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

    Abstract:

    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.

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谭桂兰,彭婧嫔,刘国维,钟李璐,袁敏.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[J].世界中医药,2022,(15).

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  • 收稿日期:2020-11-27
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  • 在线发布日期: 2022-08-23
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