文章摘要
尹 磊,傅 群,石金云,吴 晶,吴敬医.Caspase⁃1介导的焦亡在脓毒症小鼠神经元损伤中的作用研究[J].南京医科大学学报,2019,(11):1567~1570
Caspase⁃1介导的焦亡在脓毒症小鼠神经元损伤中的作用研究
Effects of Caspase⁃1⁃mediated pyroptosison on neuronal injury in sepsis mice
投稿时间:2018-09-27  
DOI:10.7655/NYDXBNS20191103
中文关键词: 脓毒症  焦亡  半胱氨酸蛋白酶⁃1  炎症因子
英文关键词: sepsis  pyroptosis  Caspase⁃1  inflammatory cytokines
基金项目:安徽省高校自然科学研究重点项目(KJ2016A730)
作者单位
尹 磊 皖南医学院第一附属医院麻醉科安徽 芜湖 241001 
傅 群 南京中医药大学附属中西医结合医院麻醉科江苏 南京 210000 
石金云 南京中医药大学附属中西医结合医院麻醉科江苏 南京 210000 
吴 晶 南京中医药大学附属中西医结合医院麻醉科江苏 南京 210000 
吴敬医 皖南医学院第一附属医院麻醉科安徽 芜湖 241001 
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中文摘要:
      目的:观察半胱氨酸蛋白酶?1(Caspase?1)介导的焦亡在脓毒症小鼠神经元损伤中的作用。方法:盲肠结扎穿孔法(cecal ligation and puncture,CLP)建立小鼠脓毒症模型。成年雄性C57BL/6小鼠90只随机分为4组:假手术+生理盐水组(Sham组,15只)、假手术+Caspase?1特异性抑制剂Ac?YVAD?CMK组(Sham+CMK组,15只)、脓毒症+生理盐水组(CLP组,30只)和脓毒症+Ac?YVAD?CMK组(CLP+CMK组,30只),术后第7天各组取6只小鼠分离脑组织,检测海马CA1区神经元损伤情况和Caspase?1阳性细胞数,以及海马组织Caspase?1、焦亡标记物Gasdermin?D蛋白(GSDMD)、白细胞介素(interleukin,IL)?1β和IL?18水平;余下小鼠术后第14天行条件恐惧性实验检测认知功能。结果:与Sham组相比,CLP组小鼠海马CA1区神经元明显损伤,Caspase?1阳性细胞数增多,海马组织中Caspase?1、GSDMD、IL?1β及IL?18含量明显升高(P < 0.05),表现为海马依赖的认知功能损伤。与CLP组相比,CLP+CMK组小鼠CA1区神经元无明显损伤,Caspase?1阳性细胞数减少,Caspase?1、GSDMD、IL?1β及IL?18含量降低,认知功能明显改善(P < 0.05)。结论:脓毒症可引起小鼠海马神经元损伤及Caspase?1介导的焦亡的激活,抑制Caspase?1介导的焦亡具有神经元保护和认知保护作用。
英文摘要:
      Objective:To observe the effects of Caspase?1?mediated pyroptosis on neuronal injury in sepsis mice. Methods:Mouse model of sepsis was established by cecal ligation and puncture(CLP)surgery. Ninety adult male C57BL/6 mice were randomly divided into four groups:Sham+saline group(n=15,Sham group),Sham + Caspase?1 inhibitorAc?YVAD?CMKgroup(N?acetyl?tyrosyl?valyl?alanyl?aspartyl chloromethyl ketone,n=15,Sham+CMK group),CLP + saline group(n=30,CLP group)and CLP+Ac?YVAD?CMK group(n=30,CLP+CMK group). Seven days after surgery,the brain of each mouse(n=6/each group)was rapidly harvested for determiningthescore of neuronal injury,number of Caspase?1?immunoreactive cells,contents of cleaved Caspase?1,pyroptosisbiomarker Gasdermin?D(GSDMD),interleukin?1β(IL?1β)and IL?18. Fourteen days after surgery,fear conditioning test was performed to evaluate the cognitive function for the rest of the mice. Results:Compared with the Sham group,the score of neuronal damage,number of Caspase?1?immunoreactive cells,contents of cleaved Caspase?1,GSDMD,IL?1β and IL?18 were significantly increased in the CLP group(P < 0.05),and mice of CLP group exhibited significant hippocampus?dependent cognitive impairment. Compared with the CLP group,increase of Caspase?1,GSDMD,IL?1β and IL?1β were inhibited by Ac?YVAD?CMK administration in the CLP+CMK group(P < 0.05). Conclusion:Sepsis induces neuronal injury and activation of Caspase?1?mediated pyroptosis in mice hippocampus,and inhibiting Caspase?1 with Ac?YVAD?CMK ameliorates sepsis?induced pyroptosis,neuronal injury and cognitive impairment.
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