Protective Effects Of Xin-Ji-Er-Kang On Anticardiovascular Remodeling In Rats With Myocardial Infarction

Background:Xin-Ji-Er-Kang?XJEK?is a formula which has been used for many years in clinic.It consists of fourteen kinds of herbal medicines,such as Panax ginseng,Ophiopogon japonicus,Astragalus mongholicus Bunge,and Polygonatum odoratum.A large number of clinical studies and basic experiments have shown that XJEK has a protective effect on coronary heart disease,myocarditis and cardiovascular remodeling.Objectives:To elucidate the beneficial effects of XJEK on myocardial infarction?MI?and cardiovascular remodeling in rats especially through the amelioration of endothelial dysfunction?ED?.Methods:136 Sprague-Dawley rats???were randomized into 13 groups:sham groups for 2,4 and 6 weeks?wk,n=10?,MI groups for 2,4 and 6wk?n=10?,XJEK groups for 2,4 and 6wk?n=10?,Fosinopril groups for 2,4 and 6wk?n=10?and control groups for 0wk?n=8?.Another 8 rats were treated for Evans blue staining and Tetrazolium chloride?TTC?stains to determine the infarct size.Cardiac function of rats in different time courses was observed by detecting changes of electrocardiogram,hemodynamic parameters and N-terminal brain natriuretic peptide content?NT-ProBNP?.Morphological changes of heart and thoracic aorta were observed by heart weight/body weight?HW/BW?,hematoxylin and eosin?HE?staining and Van Gieson?VG?staining.Enzyme-linked immunosorbent assay?ELISA?was applied to determinetetrahydrobiopterin?BH₄?,angiotensinII?AngII?,asymmetric dimethylarginine?ADMA?,endothelin-1?ET-1?and endothelial NO synthase?eNOS?content.Nitric oxide?NO?was detected by Colorimetric analysis and the total eNOS expression in cardiac tissues was detected by western blot and eNOS dimer/?dimer+monomer?ratios were detected by low temperature non-denaturing western blot.Results:The result of TTC staining showed that the infarct size of the heart was37.43±3.21%.Compared with the sham group,the hemodynamic parameters of the MI group were significantly increased at the end of 2 and 4 weeks?P<0.05?,but decreased significantly at 6 weeks?P<0.01?.XJEK administration markedly ameliorated cardiovascular remodeling?CR?,which was manifested by decreased HW/BW ratio?2,4 and 6wk,P<0.05,P<0.01?,CSA and less collagen deposition post-MI?2,4 and6wk,P<0.05,P<0.01?.XJEK administration improved cardiac function with significant inhibition of the increased hemodynamic parameters in early stage and suppression of the decreased hemodynamic parameters later.XJEK also continuously suppressed the increased NT-ProBNP content in serum of MI rats.XJEK improved ED with stimulated eNOS activities,as well as up-regulated NO levels,BH₄ content and eNOS dimer/?dimer+monomer?ratio in the cardiac tissues but down-regulated ET-1?2,4 and 6wk,P<0.05,P<0.01?,Ang II?2,4 and 6wk,P<0.05,P<0.01?and ADMA content obviously compared to sham group.Conclusion:XJEK may exert the protective effects on MI rats and could continuously ameliorate ED and reverse CR with the evolution of MI over time.