α7nAChR激动剂对脓毒症小鼠肠损伤及线粒体自噬的影响  

Effect ofα7nAChR agonist on intestinal injury and mitochondrial autophagy of sepsis mice

作　　者：费丽萍 唐坎凯[1] 刘凤琪 陈志冬[1] FEI Liping;TANG Kankai;LIU Fengqi;CHEN Zhidong(Department of Critical Care Medicine,the First People’s Hospital of Huzhou,Huzhou 313000,Zhejiang,China)

机构地区：[1]湖州市第一人民医院重症医学科,浙江湖州313000

出　　处：《中国现代医生》2025年第2期41-45,共5页China Modern Doctor

基　　金：浙江省湖州市科技局项目(2021GZ72)。

摘　　要：目的研究α7烟碱型乙酰胆碱受体(α7 nicotinic acetylcholine receptor,α7nAChR)激动剂PNU-282987对脓毒症小鼠肠损伤及线粒体自噬的影响。方法选取30只雄性C57BL/6J小鼠作为研究对象,分为对照组、模型组、PNU-282987组,每组10只。PNU-282987组在造模前1h和造模后2h分别给予1mg/kg PNU-282987腹腔注射;造模后24h取回肠组织,采用苏木精-伊红染色观察病理改变并进行Chiu’s评分,采用醋酸铀-枸橼酸铅双染色观察线粒体自噬情况,采用Western blot法检测α7nAChR、自噬标志蛋白微管相关蛋白1轻链(microtubule-associated protein 1 light chain,LC)3-Ⅱ/LC3-Ⅰ及Beclin-1、线粒体自噬相关蛋白PTEN诱导激酶(PTEN-induced kinase,PINK)1及Parkin的表达水平;取血清和回肠组织,检测白细胞介素(interleukin,IL)-1β、IL-6、IL-10。结果三组小鼠回肠组织中Beclin-1、LC3-Ⅱ/LC3-Ⅰ、PINK1、Parkin的表达水平比较,模型组小鼠高于对照组,PNU-282987组小鼠高于模型组,差异有统计学意义(P<0.05)。三组小鼠的Chiu’s评分比较,模型组小鼠高于对照组,PNU-282987组小鼠低于模型组,差异有统计学意义(P<0.05)。PNU-282987组小鼠回肠组织中α7nAChR水平高于模型组,差异有统计学意义(P<0.05)。结论α7nAChR激动剂PNU-282987改善脓毒症小鼠肠损伤,分子机制可能是激活回肠组织线粒体自噬、减轻炎症反应。Objective To investigate effects ofα7 nicotinic acetylcholine receptor(α7nAChR)agonist PNU-282987 on intestinal injury and mitochondrial autophagy in sepsis mice.Methods A total of 30 male C57BL/6J mice were divided into control group,sepsis group and PNU-282987 group,10 mice each group.In PNU-282987 group,1mg/kg PNU-282987 was injected intraperitoneally 1h before and 2h after modeling,respectively.Intestinal tissue were taken back 24h after modeling,and pathological changes were observed by hematoxylin-eosin staining and Chiu’s score were made.Mitochondrial autophagy were observed by uranium acetate-lead citrate double staining,andα7nAChR,autophagy marker protein microtubule-associated protein 1 light chain(LC)3-Ⅱ/LC3-Ⅰand Beclin-1,and mitochondrial autophagy-related protein PTEN-induced kinase(PINK)1 were detected by Western blot.Serum and ileum tissues were taken to detect interleukin(IL)-1β,IL-6,IL-10.Results Comparison of Beclin-1,LC3-Ⅱ/LC3-Ⅰ,PINK 1 and Parkin in the mice ileum tissues among three groups,model group were higher than control group,and PNU-282987 group were higher than model group,the difference were statistically significant(P<0.05).Comparison of mice in Chiu’s score among three groups,model group was higher than control group,and PNU-282987 group was lower than model group,the difference were significant(P<0.05).PNU-282987 groupα7nAChR level in the mice ileal tissue was higher than model group,the difference was significant(P<0.05).Conclusionα7nAChR agonist PNU-282987 improves intestinal injury in sepsis mice,activation of mitochondrial autophagy and reduction of inflammation in ileum may be the related molecular mechanism.

关 键 词：脓毒症 肠损伤 Α7烟碱型乙酰胆碱受体 线粒体自噬 

分 类 号：R631[医药卫生—外科学]