替米沙坦对高血压大鼠心肌纤维化的抑制作用

Inhibitory Effect of Telmisartan on Myocardial Fibrosis in Hypertensive Rats

目的探讨替米沙坦对高血压大鼠心肌纤维化的抑制作用及可能机制。方法将28只健康雄性SD大鼠随机分为空白对照组(n=7)、假手术组(n=7)及模型组(n=14)。模型组以经典的二肾一夹方法建立高血压后,随机分为模型组、替米沙坦治疗组,每组7只。治疗组灌胃给予替米沙坦(30mg/kg),其它组给予相同体积的生理盐水灌胃,1次/d。每周测量一次血压;给药8周后,麻醉处死动物并计算心脏体重指数、左心室体重指数;免疫组织化学检测心肌间质中MMP-1、TIMP-1、Ⅰ型胶原及Ⅲ型胶原的表达。结果相对于模型组,替米沙坦治疗组的收缩血压、心脏体重指数(HW/BW)、左心室体重指数(LVW/BW)明显降低(P<0.05),Ⅰ型胶原和Ⅲ型胶原的表达明显减少(P<0.05);TIMP-1的表达减少(P<0.05),而MMP-1表达增多(P<0.05)。结论替米沙坦通过减少TIMP-1的表达和增加MMP-1表达,从而抑制Ⅰ、Ⅲ型胶原的合成,缓解心肌纤维化的进程。

Objective To investigate the inhibitory effect of telmisartan on myocardial fibrosis and its possible mechanism in hypertensive rats.Methods 28 healthy male SD rats were randomly divided into blank control group,sham operation group and model group.The model group was successfully established by two kidney one clip method and then subdivided into model control group and telmisartan treated group.Telmisartan(30mg/kg)was given once a day by gavage in telmisartan treated groups,while the same volume of saline was orally given in other groups.Blood pressure was detected once a week to observe the changes.The rats were sacrificed after eight weeks of treatment and their body weight(BW),heart weight(HW)and left ventricular weight(LVM)were checked,then HW/BW(mg/g)and LVW/BW(mg/g)were calculated.Expression of MMP-1,TIMP-1 and collagen I orⅢin myocardial stroma were measured by immunohistochemistry.Results Compared with the model control group,blood pressure,HW/BW and LVW/BWwere significantly reduced in telmisartan treated group(P<0.05);also,the expression of TIMP-1,collagen I orⅢwere obviously decreased and the expression of MMP-1 was markedly increased in telmisartan treated group(P<0.05).Conclusion Treatment with telmisartan has inhibitory effect on myocardial fibrosis in hypertensive rats by reducing the expression of TIMP-1 and increasing the expression of MMP-1 to inhibit the formation of collagen I andⅢin myocardial stroma.