替米沙坦对大鼠心肌肥厚组织中Raf/MEK/ERK信号通路的影响

Effect of telmisartan on Raf/MEK/ERK single pathway in rats with myocardial hypertrophy

摘要:

目的：观察替米沙坦对心肌肥厚大鼠左室心肌组织中Raf/MEK/ERK信号通路的影响。方法：清洁级健康SD大鼠30只，随机分为对照组、模型组和干预组3组，每组10只。模型组和干预组给予异丙肾上腺素皮下注射，干预组在给予异丙肾上腺素注射同时灌胃应用替米沙坦，对照组给予生理盐水皮下注射。进行心肌相关指数、病理学检测，并采用RT-PCR方法检测大鼠左心室心肌心房钠肽（atrial natriuretic peptide，ANP）表达，检测模型建立成功情况；模型建立成功后，各组大鼠取左心室心肌组织采用免疫组化检测磷酸化Raf（phosphorylation of Raf，p-Raf）和磷酸化细胞外调节激酶1/2（phosphorylation of extracellu－lar regulated protein kinase1/2，p-ERK1/2）表达。结果：模型组p-Raf 阳性区域平均积分光密度明显高于对照组（P=0.000），干预组介于模型组与对照组之间（P=0.041，P=0.031）；模型组p-ERK1/2阳性区域平均积分光密度明显高于对照组（P=0.000），干预组介于模型组与对照组之间（P=0.0039，P=0.023）。结论：替米沙坦可能抑制p-Raf、p-ERK1/2蛋白表达而抑制Raf/MEK/ERK信号通路激活，具有抗心肌肥厚的作用。

Abstract:

Objective：To investigate the effect of telmisartan on Ras/Raf/ERK1/2 signal pathway in rats with myocardial hypertrophy. Methods：Totally 30 rats were randomly divided into 3 groups including control group，model group and intervention group. Each group has 10 rats. Hypodermic injection of normal saline was applied in control group；hypodermic injection of isoproterenol was ap－plied in model group；hypodermic injection of isoproterenol and telmisartan was applied in intervention group. Myocardial index and pathological detections were performed. RT-PCR assay was used to detect ANP mRNA expression. After the model was successfully made，rats’ left cardiac tissues were collected and p-Raf protein and p-ERK1/2 protein expression was detected by immunohis－tochemistry. Results：Average integral optical density in p-Raf positive area was the highest in model group（P=0.000） followed by intervention group and control group（P=0.041，P=0.031）. Average integral optical density in p-ERK1/2 positive area was the highest in model group（P=0.000） followed by intervention group and control group（P=0.0039，P=0.023）. Conclusions：Telmisartan resists my－ocardial hypertrophy since it can reduce expressions of Raf protein and ERK1/2 and inhibit the activation of Raf/MEK/ERK signal pathway