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内质网应激在肥胖高血压大鼠心肌重构中的作用
作者:芦波  谢君  符德玉  周训杰  张艳芝  陈晓喆  赵铭一  桂明泰  姚磊  李建华 
单位:上海中医药大学附属岳阳中西医结合医院 心内科/心血管研究室, 上海 200437
关键词:自发性高血压 肥胖 内质网应激 心肌重构 细胞凋亡 大鼠 
分类号:R544.1
出版年·卷·期(页码):2021·49·第九期(1030-1036)
摘要:

目的:观察内质网应激在肥胖高血压大鼠心肌重构中的作用。方法:5周龄雄性自发性高血压大鼠(SHR)高脂饮食制备肥胖高血压大鼠模型(OBH组),以年龄、性别匹配的WKY大鼠和SHR作为WKY组和SHR组,10周后观察体重、心脏重量、左室重量、血压,使用小动物超声测定心脏超声,测定血清和心肌血管紧张素Ⅱ(Ang Ⅱ)含量,TUNEL检测心肌细胞凋亡,Western blot和实时聚合酶链反应(RT-PCR)测量内质网应激分子表达水平。结果:(1) OBH组Lee's指数及肝脏重量指数高于其余两组(P<0.05),OBH组和SHR组收缩压(SBP)大于WKY组(P<0.05);(2) OBH组和SHR组血清、心肌Ang Ⅱ水平均高于WKY组(P<0.05);(3) OBH组、SHR组左室重量指数(LVMI)和矫正的左室重量指数(LVMI-cor)显著高于WKY组(P<0.05);(4) OBH组心肌GRP78、CHOP、Caspase 12的mRNA水平显著高于SHR组和WKY组(P<0.05),SHR组显著高于WKY组(P<0.05),OBH组、SHR组ATF6的mRNA水平显著高于WKY组(P<0.05);(5) OBH组心肌GRP78、CHOP、Caspase 12蛋白表达水平高于WKY组和SHR组(P<0.05),OBH组ATF6蛋白表达水平显著高于WKY组(P<0.05)。结论:OBH大鼠心肌重构可能与内质网应激下游CHOP、Caspase 12凋亡信号通路的激活相关。

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