[1]孟 哲,腾 帅,王 琛,等.积雪草酸通过激活Nrf2抗氧化通路抑制自发性高血压大鼠心肌纤维化[J].中国药理学通报,2018,(08):1073-1077.[doi:10.3969/j.issn.1001-1978.2018.08.009]
 MENG Zhe,TENG Shuai,WANG Chen,et al.Asiatic acid inhibits cardiac fibrosis via activating Nrf2-mediated anti-oxidant signaling pathway in spontaneous hypertensive rats[J].Chinese Pharmacological Bulletin,2018,(08):1073-1077.[doi:10.3969/j.issn.1001-1978.2018.08.009]
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积雪草酸通过激活Nrf2抗氧化通路抑制自发性高血压大鼠心肌纤维化()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1073-1077
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
Asiatic acid inhibits cardiac fibrosis via activating Nrf2-mediated anti-oxidant signaling pathway in spontaneous hypertensive rats
文章编号:
1001-1978(2018)08-1073-06
作者:
孟 哲腾 帅王 琛白雪洋李海禹
郑州大学第一附属医院心血管内科,河南 郑州 450052
Author(s):
MENG ZheTENG ShuaiWANG ChenBAI Xue-yangLI Hai-yu
Dept of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China
关键词:
积雪草酸 心肌纤维化 氧化应激 核因子E2相关因子2 自发性高血压大鼠 Akt/GSK-3β/Fyn信号通路
Keywords:
asiatic acid cardiac fibrosis oxidative stress nuclear factor E2 related factor 2 spontaneous hypertensive rats Akt/GSK-3β/Fyn signaling pathway
分类号:
R-332; R284.1; R322.11; R329.25; R544.1; R542.23; R977.6
DOI:
10.3969/j.issn.1001-1978.2018.08.009
文献标志码:
A
摘要:
目的 探讨积雪草酸(asiatic acid,AA)对自发性高血压大鼠(spontaneous hypertensive rats,SHRs)心肌纤维化的拮抗作用及其可能的分子机制。方法 动物分为4组:对照组(Wky)、SHRs组、SHRs +AA组(SHRs+AA 20 mg-1·kg-1·d-1)、AA组(Wky+AA 20 mg-1·kg-1·d-1),每组10只。天狼星红染色法观察胶原蛋白沉积水平; 比色法测定各组氧化应激水平; Western blot法测定相关蛋白表达。结果 AA能有效减少心肌胶原蛋白沉积,以及PAI-1、CTGF、Collagen I、FN的表达,提高血清中SOD、T-AOC活性,并降低MDA含量,增强心肌组织Akt、GSK-3β磷酸化,抑制Fyn核转位; 提高Nrf2活性,并增加NQO1、HO-1蛋白表达。结论 AA能有效抑制SHRs心肌纤维化,其机制可能通过激活Nrf2诱导的抗氧化通路,上调心肌组织抗氧化活性,进而减少氧化应激产物形成。
Abstract:
Aim To explore whether asiatic acid(AA)inhibits cardiac fibrosis,the common but irreversible pathological phenomenon caused by different cardiovascular diseases in spontaneous hypertension rats(SHRs)and its probable molecular mechanism.Methods Rats were divided into four groups:control group(Wistar Kyoto rats,Wkys,n=10),SHRs group(SHRs,n=10),SHRs+AA group(SHRs+AA 20 mg-1·kg-1·d-1,n=10),and AA group(Wkys+AA 20 mg-1·kg-1·d-1,n=10).The level of collagen deposition was measured by Sirius red staining.The concentration of malondialdehyde(MDA),superoxide dismutase(SOD),and total antioxidant capacity(T-AOC)were measured by colorimetry.The protein expressions of plasminogen activator inhibitor-1(PAI-1),connective tissue growth factor(CTGF),collagen I(Col I),fibronectin(FN),nuclear factor E2 related factor 2(Nrf2),quinone oxidoreductase(NQO1),hemeoxygenase-1(HO-1),p-Akt,p-GSK-3β and Fyn were measured by Western blot.Results AA could reduce the level of collagen deposition and the expression of CTGF,PAI-1,Col Ⅰ and FN.AA suppressed the production of MDA,but elevated the activity of SOD and T-AOC.AA also up-regulated the nuclear translocation of Nrf2 and the expression of NQO1 and HO-1.Furthermore,AA increased the phosphorylation of Akt and GSK-β,and inhibited nuclear translocation of Fyn.Conclusion AA could partially inhibit cardiac fibrosis in SHRs,which is probably dependent on up-regulating Nrf2-mediated oxidant signaling pathway.

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备注/Memo

备注/Memo:
收稿日期:2018-04-19,修回日期:2018-05-20
基金项目:河南省卫生厅科技攻关项目(No 201403051)
作者简介:孟 哲(1983-),男,博士,主治医师,研究方向:高血压和冠心病的发病机制,E-mail:mengzhenihao@163.com;
李海禹(1983-),男,博士,副主任医师,研究方向:冠心病和高血压的药物治疗,通讯作者,E-mail:lihaiyu156239@126.com
更新日期/Last Update: 2018-07-26