坎地沙坦对去甲肾上腺素诱导的大鼠心肌重塑的作用

Effect of Candesartan on Cardiac Remodeling of Rats by Norepinephrine

目的研究去甲肾上腺素(NE)诱导的左室肥厚大鼠心肌重塑中基质金属蛋白酶(MMP-13)及其生理性抑制剂TIMP-1的作用及坎地沙坦的作用。方法雌性W istar大鼠29只,随机分为3组:①对照组;②NE组[1.2mg/(kg.d)×15d];③NE+坎地沙坦组[2mg/(kg.d)×15d]。NE腹腔注射,2次/d,连续15d,建立左室肥厚模型。应用超声心动图及病理学方法评价心肌肥厚和心肌间质胶原的表达,用免疫组织化学法和图像分析技术检测心肌MMP-13、TIMP-1和间质胶原蛋白的表达。结果大鼠腹腔注射NE后发生左室肥厚和心肌纤维化。与对照组相比,NE组心肌MMP-13表达减少(P<0.05),而心肌TIMP-1和Ⅰ型、Ⅲ型胶原蛋白表达、胶原容积分数均上升(P<0.05)。坎地沙坦组室间隔厚度、心肌间质胶原的表达均降低,TIMP-1/MMP-13比值降低。结论MMP-13、TIMP-1参与了NE诱导的左室肥厚大鼠心肌重塑过程,坎地沙坦能使MMP-13/TIMP-1正常化而抑制心肌重塑的发展。

Objective To investigate the role of Matrix Metalloproteinases（ MMP - 13） , tissue inhibitor of metalloproteinase （TIMP - 1 ） in cardiac remodeling of rat by norepinephrine （NE） and the effects of candesartan on it. Methods 29 female Wistar rats were randomly divided into three groups： ①control group, ② NE group [ 1.2mg/（kg ·d）×15d], ③NE ＋ candesartan group [2mg/（kg ·d）×15d]. The rat cardiac hypertrophy models were established by intraperitoneal injection of NE twice a day for 15 days. Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination. The protein expression of MMP - 13, TIMP - 1 ,type Ⅰ ,type Ⅲ Collagen were examined by immunhistochemical analysis. Results NE - induced cardiac hypertrophy and cardiac fibrosis occurred in the left ventricular . The protein expression of MMP - 13 decreased（ P 〈0.05） , at the same time , TIMP - 1 ,type Ⅰ ,type m Collagen and collagen volume fraction（CVF） all sharply increased（ P 〈0.05）. After candesartan treatment, the interventricular septal thickness ,CVF,type Ⅰ ,type m Collagen and expression of TIMP- 1 decreased and the expression of MMP - 13 elevated（ P 〈0.05）. Conclusion MMP - 13 ,TIMP - 1 are involved in the cardiac remodeling induced by NE . Candesartan can prevent cardiac fibrosis, which is associated with myocardial MMP- 13 and TIMP- 1.