心肌自噬在肾去神经联合氨氯地平治疗高血压大鼠心肌肥厚中的作用

The role of cardiac autophay on renal denervation combined with amlodipine treating myocardial hypertrophy

目的探讨心肌自噬在肾去神经联合氨氯地平治疗大鼠高血压心肌肥厚的作用。方法以12周雄性自发性高血压大鼠构建高血压心肌肥厚动物模型为研究对象,分为假手术组(A组)、双侧肾动脉去神经+空白药物对照组(B组)、双侧肾动脉去神经+氨氯地平组(C组)。联合治疗后4周,RT-PCR法检测心肌组织肥厚基因的表达,测定左室质量指数(LVMI),行组织病理切片HE染色和Western blot测定自噬活性标志蛋白的表达。结果心脏组织的病理切片和肥厚基因表达变化显示,与A组比较,B组及C组的心脏体积减小、室壁变薄,肥厚相关基因心房钠尿肽(ANP)和β-肌球蛋白重链(β-MHC)表达下降;同时,LVMI显示同样的结果。自噬标志蛋白微管相关蛋白1轻链3(LC3)和多功能泛素化结合折叠蛋白(SQSTM1/p62)的表达结果显示,与A组比较,B组及C组的心肌自噬标志蛋白LC3(LC3Ⅱ/Ⅰ)表达下调,p62表达上调,且C组更明显。结论心肌自噬活性的改变在肾脏去神经联用氨氯地平治疗高血压相关性心肌肥厚中起到重要的作用。

Objective To explore the effects of cardiac autophagy on renal denervation combined with amlodipine treating hypertension-related myocardial hypertrophy in spontaneous hypertension rats(SHR).Methods The models of hypertension-related myocardial hypertrophy were constructed by twelve-week male SHRs,and divided into three groups:the sham-operated group(A group),bilateral renal artery denervation combined with blank drug treatment(B group)and bilateral renal artery denervation combined with amlodipine treatment(C group).After 4 weeks postsurgery combined with drugs treatment,the expression of hypertrophy-related gene was detected by RT-PCR,left ventricular mass index was calculated,histological sections were stained with HE and the expression of autopahgic actvity mark proteins were detected by Western blot.Results At the end of 4 weeks after postsurgery,compared with A group,the result of histological sections and hypertrophy-related gene expression(β-MHC and ANP)reduced in B group and C group.Moreover,the data of left ventricular mass index showed similar results.The autophagy-related protein data showed that compared with A group,LC3Ⅱ/Ⅰwas significantly decreased,but the p62 was significantly increased in B group and C group,and the data in C group was particularly obvious.Conculsion Renal denervation combined with amlodipine can inhibit hypertension-related myocardial hypertrophy,and its’mechanism may be related with altering autophagic activity.