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。
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 expres sion 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.
作者
孟哲
腾帅
王琛
白雪洋
李海禹
MENG Zhe;TENG Shuai;WANG Chen;BAI Xue-yang;LI Hai-yu(Dept of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Chin)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第8期1073-1078,共6页
Chinese Pharmacological Bulletin
基金
河南省卫生厅科技攻关项目(No 201403051)
