ABSTRACT
Objective Based on animal model of left ventricular pressure overload induced cardiac fibrosis,to investigate the specific role and molecular mechanism of KLF15 gene in this process.Methods To establish rat animal model of pressure overload induced cardiac hypertrophy by aortic coarctation under non artificial ventilation conditions,and then release the constriction,to observe the rat heart color Doppler images,myocardial interstitial fibrosis features and protein expression level changes of KLF15、Transforming growth factor-β (TGF-β) 、Connective tissue growth factor (CTGF)、Myocardin-related transcription factor A(MRTF-A) in overload-unload corresponding time points.Results We successfully completed aortic banding and debanding operations by use of SD rats without artificial ventilation.Through color Doppler echocardiography detection,from images to know:the effect of constriction and loosening is definite.The expression of collagen type Ⅰ,collagen type Ⅲ,TGF-β,CTGF,MRTF-A were significantly higher and myocardial hypertrophy was aggravated but the KLF15 protein expression level was significantly lower in pressure overloaded rats than in Sham rats(all P ＜ 0.05).All values were in an increasing tendency with the constrictive time prolonged (P ＜ 0.05).The response to unloading was opposite,the sooner to loose the better to the recovery to normal.The differences of indicators are very notable (P ＜ 0.05).Conclusion By feedback regulation TGF-β,KLF15 inhibited the effect of CTGF and MRTF-A,reducing myocardial interstitial fibrosis.
ABSTRACT
Objective To investigate the cardioprotective effect of losartan o n subtotal nephrectomy renal failure rats. Methods Renal failure rats were estab lished by subtotal nephrectomy, and then divided into RF group with subtotal nep hrectomy,RF+Los group with additional losartan(10 mg?kg-1?d-1) gavage. Rats underwent sham operation(sham group) with normal saline gavage as control. Hear t changes of experimental rats were observed 12 weeks after operation. Results T he RF group developed hypertension of arterial systolic blood pressure(SBP) and myocardiac myocytes hypertrophy. The levels of collagen type Ⅰ,type Ⅲ,and fi bronectin in endocardium and surrounding intracardial coronary arteries adventit ia of the RF group were significantly increased as compared to those of the sham group. The SBP and the levels of collagen type Ⅰ,Ⅲand fibronectin were marked ly decreased in the RF+Los group as compared to those of the RF group.Expressio n of angiotensin Ⅱsubtype 1 receptor (AT1R) mRNA in the myocardium of the RF+L os group was significantly down regulated as compared to that of RF group. Concl usions Losartan can prevent the cardiac ventricular remodeling with left ventric ular hypertrophy (LVH) and myocardial interstitial fibrosis by the depression of renin-angiotensin system through the down-regulation of myocardiac AT1R mRNA.