坎地沙坦对高血压大鼠左室重构的抑制作用

Protective effects of candesartan against left ventricular remodeling

目的:研究坎地沙坦对大鼠心肌组织中钙网蛋白(CRT)及细胞凋亡蛋白caspase-12表达的影响及其对左室重构的逆转作用。方法:采用双肾双夹术建立高血压大鼠模型。将36只雄性SD大鼠随机分为假手术组、手术组和坎地沙坦干预组,每组12只(n=12)。喂养6周后,通过颈动脉插管测定大鼠平均动脉压(MBP);称量大鼠的体质量(BW)、心脏质量(HW)、左心室质量(LVW),计算心脏质量指数(HW/BW)及左心室质量指数(LVWI=LVW/BW)。采用免疫组化染色法检测大鼠心肌组织中CRT及caspase-12表达的水平。结果:与假手术组比较,手术组大鼠的MBP、LVWI均有显著升高(P<0.05),内质网应激相关分子CRT及caspase-12蛋白的表达水平均增强。与手术组比较,坎地沙坦干预组大鼠的MBP和LVWI均降低(P<0.05),内质网应激相关分子CRT及caspase-12蛋白的表达水平均减弱。结论:高血压触发的内质网应激可能参与了高血压后期的左室重构过程。而坎地沙坦干预后内质网应激水平明显降低且心室重构在一定程度上得到逆转,提示坎地沙坦可能通过降低CRT和caspase-12介导的内质网应激反应起到抑制高血压左室重构的作用。

AIM： To investigate the influence of candesartan on the expression of CRT and caspase-12 in rat myocardial tissues and its effects against left ventricular remodeling.METHODS： Thirty-six male Sprague Dawley（SD） rats were equally randomized into sham group,double renal artery double clip group and candesartan intervention group [5 mg/（kg·day）] per gavage.Six weeks later,mean arterial pressure（MAP） was measured,body weight,whole heart weight,left ventricular weights,HW/BW and LVWI were obtained,and expressions of CRT and caspase-12 in rat myocardial tissues were examined by immunohistochemistry.RESULTS： MAP,HW/BW,LVWI and expressions of CRT and caspase-12 in myocardial tissues remarkably increased in double renal artery double clip group compared with those in sham group（P〈0.05）.However,candesartan significantly decreased MBP,HW/BW and LVWI,and downregulated the expressions of CRT and caspase-12 in myocardial tissues（P〈0.05）.CONCLUSION： Endoplasmic reticulum stress may be involved in left ventricular remodeling caused by renal artery double-clip hypertension.Candesartan may exert some protective effect on the heart by inhibiting the endoplasmic reticulum stress via downregulating the expression of CRT and caspase-12.