厄贝沙坦对高血压大鼠心肌纤维化的影响  

Effect of Irbesartan on the Impact of Myocardial Fibrosis in Hypertensive Rats

作　　者：李勇[1] 熊世熙[1] 周慧芬[2] 

机构地区：[1]武汉大学中南医院,湖北武汉430071 [2]咸宁学院基础医学院病理学教研室

出　　处：《咸宁学院学报（医学版）》2009年第5期373-375,共3页Journal of Xianning Univarsity(medical Sciences)

摘　　要：目的通过观察厄贝沙坦对高血压大鼠血压、心脏指数、基质金属蛋白酶1及其抑制剂(MMP-1/TIMP-1)、Ⅰ、Ⅲ型胶原表达的影响,探讨厄贝沙坦对高血压大鼠心肌纤维化的可能保护机制。方法将21只健康雄性SD大鼠随机分为空白对照组(n=7)及模型组(n=14),模型组以经典的二肾一夹方法建立。模型建立成功后,随机分为模型对照组、厄贝沙坦治疗组,每组7只。治疗组予厄贝沙坦(50mg/kg)灌胃给药,空白对照组及模型对照组给予相同体积的生理盐水灌胃,每日1次。给药8周后,麻醉处死动物,称取心脏(HW)和左心室(含室间隔LVW)重量,计算HW/BW为心脏指数(mg/g),LVW/BW为左心室指数(mg/g)。用SP免疫组化法检测心肌间质中MMP-1/TIMP-1、Ⅰ型及Ⅲ型胶原的表达。结果与空白对照组相比,模型组的血压、HW/BW、LVW/BW明显升高(P<0.05);与模型组相比,厄贝沙坦治疗组的血压、HW/BW、LVW/BW明显降低(P<0.05)。与空白对照组相比,模型组TIMP-1、Ⅰ型及Ⅲ型胶原表达明显增多,MMP-1表达减少(P<0.05);与模型对照组相比,治疗组的TIMP-1、Ⅰ型及Ⅲ型胶原的表达明显减少(P<0.05),MMP-1表达增多。结论厄贝沙坦可以增加MMP-1和减少TIMP-1的表达,抑制Ⅰ、Ⅲ型胶原的生成从而改善心肌纤维化。Objective Through the observation of irbesartan in hypertensive rats blood pressure, cardiac index, matrix metalloproteinase-1 and its inhibitor （MMP-1/TIMP-1）,Ⅰ ,Ⅲ collagen expression, and to explore irbesartan in hypertensive myocardial fibrosis may be protective mechanismso Methods To 35 healthy male SD rats were randomly divided into blank control group （ n = 7 ） and model group （ n = 14）, model group to the classic two-kidney one clip methods. After the success of model building were randomly divided into model control group, irbesartan treatment groups, each with seven. Irbesartan treatment group Ⅰ （50mg/kg） intragastric administration, blank control group and model control group was given the same volume of saline given orally once a day. Eight weeks after delivery, anesthesia animals were killed, saying that taking the heart （HW） and left ventricle （including septum LVW） weight, calculated HW / BW as the cardiac index （mg / g）, LVW/BW as a left ventricular index （mg/g）. With SP immunohistochemical detection of myocardial interstitial MMP-1/TIMP-1, Ⅰ-type collagen and the expression of collagen type Ⅲ. Results Compared with the blank control group, model group, blood pressure, HW/BW, LVW/BW was significantly higher （ P 〈 0.05 ） ;with model group, compared with irbesartan treatment group, blood pressure, HW/BW, LVW/BW was significantly lower （P 〈 0.05 ）. Compared with the blank control group, model group, TIMP-1, Ⅰ-type collagen and collagen type Ⅲ expression was significantly increased, MMP-1 expression was decreased （ P 〈 0.05 ） ; with the model control group, treatment group TIMP-1 , Ⅰ-type collagen and collagen type Ⅲ expression was significantly reduced （P 〈 0.05）, MMP-1 expression increased. Conclusion Irbesartan can increase MMP-1 and reduced the expression of TIMP-1, inhibit Ⅰ, Ⅲ collagen formation thereby improving myocardial fibrosis. Com- pared with the model control group, treatment group TIMP-1, Ⅰ-type collagen and

关 键 词：高血压 心肌纤维化 基质金属蛋白酶1 基质金属蛋白酶1抑制剂 厄贝沙坦 

分 类 号：R965.1[医药卫生—药理学]