替米沙坦对心肌梗死后心力衰竭大鼠左心室非梗死区激活素A及其受体表达的影响

摘要

目的:探讨替米沙坦对心肌梗死后心力衰竭(心衰)大鼠左心室非梗死区激活素A及其受体表达的影响,阐明替米沙坦改善心肌胶原沉积的可能机制.方法:27只Wister大鼠分为假手术组(7只)、模型组(10只)和替米沙坦组(10只).模型组和替米沙坦组大鼠结扎左冠状动脉前降支,假手术组大鼠左冠状动脉前降支仅穿线不结扎.建模后饲养5周,每组存活6只大鼠.假手术组大鼠给予0.5% CMC(10 mL·kg-1),模型组大鼠给予0.5%CMC(10 mL·kg-1),替米沙坦组大鼠给予替米沙坦(30 mg·kg-1);连续灌胃给药4周后测定大鼠全心肥厚指数及左心室肥厚指数,RT-PCR 法测定大鼠左心室非梗死区心肌组织中激活素A、激活素 Ⅱ型A受体(ActR ⅡA)、Ⅱ型B受体(ActR ⅡB)、Ⅰ型胶原蛋白(ColⅠ)和Ⅲ型胶原蛋白(ColⅢ)mRNA 表达水平以及ColⅠ/ ColⅢ比值;免疫组织化学染色观察大鼠左心室非梗死区心肌组织中激活素A蛋白的表达强度.结果:与假手术组比较,模型组大鼠全心肥厚指数和左心室肥厚指数明显升高(P<0.01),激活素A、ActRⅡA、ActRⅡB、ColⅠ和ColⅢ mRNA 表达水平以及ColⅠ/ColⅢ比值升高(P<0.01).免疫组织化学染色,假手术组大鼠非梗死区心肌组织中激活素A蛋白呈低水平表达,模型组大鼠非梗死区心肌组织中激活素A蛋白呈高水平表达.结论:替米沙坦可能通过下调激活素A及其受体的表达水平改善心衰过程中心肌胶原沉积.%Objective:To investigate the effects of telmisartan on the expressions of activin A and its receptors in non-infarction area of left ventricle in the heart failure rats after myocardial infarction,and to clarify the mechanism of improvement effect of telmisartan on myocardial collagen deposition.Methods:A total of 27 rats were divided into sham operation group(n=9),model group(n=20) and telmistartan group(n=10).The left anterior descending coronary arteries of the rats in model group and telmisartan groupwere ligated,and the left anterior descending coronary arteries of the rats in sham operation group were not ligated.After 5 weeks,there were 6 surviving rats in each group.The rats in sham operation group were treated with 0.5%CMC(10 mL·kg-1),the rats in model group were treated with 0.5%CMC (10 mL·kg-1),and the rats in telmisartan group were treated with telmisartan (30 mg·kg-1).All the rats were treated with medicines by intragastric administration for 4 weeks.The whole cardiac hypertrophy index and left ventricular hypertrophy index of the rats were measured;the mRNA expression levels of activin A,ActRⅡA,ActRⅡB,ColⅠ,and ColⅢ in the non-infarction areaof the rats were detected by RT-PCR and the ratio of ColⅠ/ ColⅢ was calculated;the expression intensities of activin A protein in the myocardium tissue in non-infarction area of the rats in various groups were observed by immunohistochemical staining.Results:Compared with sham operation group,the whole cardiac hypertrophy index and left ventricular hypertrophy index of the rats in model group were significantly increased (P<0.01);the mRNA expression levels of activin A,ActRⅡA and ActRⅡB,ColⅠ,ColⅢ and the ratio of ColⅠ/ColⅢ were also increased (P<0.01).The immunohistochemical staining results showed that the expression level of activin A protein in noninfarction area of left ventricle of the rats in sham operation group was lower,and the expression level of activin A protein in non-infarction area of left ventricle of the rats in model group was higher.Conclusion:Telmisartan may improve the myocardial collagen deposition by inhibiting the expressions of activin A and its receptors during heart failure.