激动ALDH2抑制程序性坏死减轻脓毒症小鼠心肌损伤的作用探讨  

Effect of activating ALDH2 on inhibiting programmed necrosis to alleviate myocardial injury in septic mice

作　　者：张共鹏 魏艳龙 黄毓慧 李文韬 程志鹏 高琴[2] 王佳慧 叶红伟[2] Zhang Gongpeng;Wei Yanlong;Huang Yuhui;Li Wentao;Cheng Zhipeng;Gao Qin;Wang Jiahui;Ye Hongwei(School of Clinical Medicine,Bengbu Medical College,Bengbu 233000,Anhui,China;Department of Physiology,Bengbu Medical College,Bengbu 233000,Anhui,China;Department of Anatomy,Bengbu Medical College,Bengbu 233000,Anhui,China)

机构地区：[1]蚌埠医学院临床医学院,安徽蚌埠233000 [2]蚌埠医学院生理学教研室,安徽蚌埠233000 [3]蚌埠医学院解剖学教研室,安徽蚌埠233000

出　　处：《右江民族医学院学报》2022年第6期829-834,共6页Journal of Youjiang Medical University for Nationalities

基　　金：国家级大学生创新创业项目(202010367061)。

摘　　要：目的观察脓毒症小鼠心肌损伤中程序性坏死的发生,探讨线粒体乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)是否通过抑制程序性坏死发挥心肌保护作用。方法选取8周龄雄性C57BL/6J小鼠,采用CLP法诱导脓毒症心肌损伤模型。将小鼠随机分为3组(10只/组):假手术组(Sham组)、脓毒症组(CLP组)、脓毒症+Alda-1组(CLP+Alda-1组)。CLP术后24 h,HE染色观察心肌损伤,透射电镜观察心肌超微结构变化;用ELISA法测定心肌组织肿瘤坏死因子-α(TNF-α)含量;Western Blot法检测心肌组织ALDH2、Caspase-8、RIPK1、RIPK3蛋白表达。结果与Sham组相比,CLP组小鼠HE染色显示心肌纤维排列不整齐,有炎症细胞浸润,间质水肿,红细胞渗出;透射电镜观察到心肌线粒体肿胀,嵴减少,外膜破裂;心肌组织TNF-α含量升高(P<0.01),Caspase-8蛋白表达降低(P<0.05),RIPK1和RIPK3蛋白表达升高(P<0.01)。与CLP组相比,CLP+Alda-1组小鼠心肌形态有改善,线粒体损伤减轻;心肌组织TNF-α水平降低(P<0.05),ALDH2和Caspase-8蛋白表达升高(P<0.05),RIPK1和RIPK3蛋白表达降低(P<0.01或P<0.05)。结论小鼠脓毒症心肌损伤时伴有程序性坏死的发生,Alda-1激动ALDH2可通过抑制程序性坏死减轻心肌损伤。Objective To observe the occurrence of programmed necrosis in myocardial injury of septic mice,and to investigate whether aldehyde dehydrogenase 2(ALDH2)plays a protective role in myocardium by inhibiting programmed necrosis.Methods Male C57BL/6J mice aged 8 weeks were selected to be induced into the model of septic myocardial injury by the CLP(cecal ligation and puncture)method.The mice were randomly divided into 3 groups(10 mice/group):the sham group(Sham),the sepsis group(CLP)and the sepsis+Alda-1 group(CLP+Alda-1).Twenty-four hours after CLP operation,the myocardial injury was observed by HE staining and the myocardial ultrastructure was observed by transmission electron microscopy.The content of tumor necrosis factor-α(TNF-α)in myocardial tissue was determined by ELISA.The expressions of protein ALDH2,Caspase-8,RIPK1 and RIPK3 in myocardium were detected by Western Blot.Results Compared with the sham group,the CLP group showed in HE staining irregular arrangement of myocardial fibers,infiltration of inflammatory cells,interstitial edema,and exudation of red blood cells.Transmission electron microscopy showed that myocardial mitochondrial swelling,cristae reduction and rupture of outer membrane occured in the CLP group.And there was increase in the TNF-αin myocardial tissues(P<0.01),decrease in the protein expression of Caspase-8(P<0.05),and rise in the expressions of protein RIPK1 and RIPK3(P<0.01).Compared with the CLP group,the CLP+Alda-1 group had myocardial morphology improved,mitochondrial damage alleviated,TNF-αlevel decreased in myocardial tissues(P<0.05),expressions of ALDH2 and Caspase-8 increased(P<0.05),and expressions of RIPK1 and RIPK3 decreased(P<0.01 or P<0.05).Conclusion Myocardial injury in mice with sepsis is accompanied by programmed necrosis,and activation of ALDH2 with Alda-1 can alleviate myocardial injury via inhibiting programmed necrosis.

关 键 词：脓毒症 心肌疾病 坏死 乙醛脱氢酶2 线粒体 

分 类 号：R345.42[医药卫生—基础医学]