替米沙坦对心肌梗死后大鼠纤溶系统的影响

Effects of Telmisartan on fibrinolytic system function in experimental rats with acute myocardial infarction

目的探讨替米沙坦对心肌梗死(MI)后大鼠纤溶系统的影响及其机制。方法采用左冠脉前降支结扎法构建大鼠MI模型。建模及给药14 d后,测定大鼠血浆及主动脉组织匀浆血管紧张素Ⅱ(AngⅡ)水平、大鼠血浆和血管孵育液纤溶酶原激活物抑制剂-1(PAI-1)和组织型纤溶酶原激活剂(tPA)活性及tPA/PAI-1比值、主动脉血管条同位素3H标记的胸腺嘧啶(3H-TdR)掺入率、磷酸化胞外信号调节激酶(p-ERK1/2)和血管紧张素受体1(AT1R)蛋白在血管组织的表达。结果替米沙坦组心肌病理改变明显减轻。与假手术组比较,MI组血浆和主动脉组织匀浆AngⅡ含量、血浆和主动脉孵育液PAI-1活性均明显增高(P均<0.05)而血浆和主动脉孵育液tPA活性及tPA/PAI-1比值均明显降低(P均<0.05);与MI组比较,替米沙坦组主动脉组织匀浆AngⅡ含量、血浆和主动脉孵育液PAI-1活性均显著降低(P均<0.05),但血浆AngⅡ含量、血浆和主动脉孵育液tPA活性及tPA/PAI-1比值均明显增高(P均<0.05)。与假手术组比较,MI组主动脉匀浆p-ERK1/2及AT1R蛋白的表达均显著增加(P<0.05);与MI组比较,替米沙坦组主动脉血管组织3H-TdR掺入率及p-ERK1/2和ATlR蛋白表达均显著降低(P均<0.05),但血浆AngⅡ含量、血浆和主动脉孵育液tPA活性及tPA/PAI-1比值均明显增高(P均<0.05)。结论 MI大鼠存在纤溶系统功能紊乱,替米沙坦可能通过AT1R作用经ERK信号通路调控纤溶活性从而改善大鼠MI后的纤溶系统功能。

Objective To explore the effects of telmisartan,a AT1R blocker（ARB）,on the fibrinolytic system function both at the plasma and local vascular tissue in rats with myocardial infarction（MI） and possible mechanisms.Methods The rat model of MI was achieved by left anterior descend coronary artery ligation.24 male SD rats were randomly divided into sham-operated,MI and telmisartan groups（n=8）.At the 14th day after MI,AngⅡ levels of plasma and homogenized aortic tissue in rats were measured by radioimmunoassay while the activity of PAI-1 and tPA in the plasma and incubation solution for aorta in rats was determined by spectrophotometric assay,and the expression of p-ERK1/2 and AT1R proteins in homogenized aortic tissue were examined by Western blot.Results The myocardium in sham-operated group was normal but abnormal injured myocardium in MI group,and the damaged myocardium induced by MI was remarkably improved in telmisartan group.Compared with sham-operated group,AngⅡ levels in the plasma and homogenized aortic tissue and PAI-1 activity in the plasma and incubation solution for aorta were significantly increased but the activity of tPA and the ratio of tPA to PAI-1 in the plasma and incubation solution for aorta decreased remarkably in MI group（all P0.05）.Compared with MI group,AngⅡ levels in homogenized aortic tissue,the activity of PAI-1 in the plasma and incubation solution for aorta were markedly reduced but AngⅡ levels in the plasma,tPA activity and the ratio of tPA to PAI-1 enhanced notably in the plasma and incubation solution for aorta in telmisartan group（all P0.05）.Compared with sham operated group,the expression of P-ERK,AT1R and the incorporate rate of 3H-TdR into the vascular wall of rats were significantly increased in MI group.Compared with MI group,the three indexes were significantly decreased in telmisartan group（all P0.05）.Conclusions The fibrinolytic system function is abnormal in MI rats and the treatment with ARB-telmisartan can improve the abnormal fibrinolytic system function in MI rats through inhibiting rennin angiotensin system and ERK cellular signal pathways.