Iduna调控Hippo/YAP通路抑制炎症反应从而减轻围术期小鼠的神经认知障碍  

Iduna attenuates perioperative neurocognitive disorder in mice via Hippo/YAP pathway

作　　者：李霞[1] 尚国政 高宇博[1] LI Xia;SHANG Guozheng;GAO Yubo(Department of Anesthesiology,General Hospital of Ningxia Medical University,Yinchuan 750001,China)

机构地区：[1]宁夏医科大学总医院麻醉与围术期医学科,宁夏银川750001

出　　处：《中国病理生理杂志》2023年第3期409-416,共8页Chinese Journal of Pathophysiology

基　　金：宁夏留学回国人员创新创业项目(宁人社函[2021]5号);宁夏自然科学基金项目(No.2019AAC03218)。

摘　　要：目的:探讨Iduna对老龄小鼠围术期神经认知障碍(PND)过程中炎症因子的影响并分析Hippo/YAP信号通路在此发挥的作用。方法:取20只C57BL/6老龄小鼠分为对照(control)组和模型(model)组(行剖腹探查术诱导建立PND小鼠模型),每组10只,用荧光定量PCR检测PND小鼠脑组织中Iduna的mRNA水平。在PND造模前,通过侧脑室注射Iduna过表达腺相关病毒(AAV)载体、sh-Iduna AAV载体和(或)Hippo/YAP信号通路抑制剂CA3。将40只C57BL/6老龄小鼠分为control+AAV9-Con组、control+AAV9-Iduna组、model+AAV9-Con组和model+AAV9-Iduna组,每组10只,在造模后7 d,用水迷宫实验检测动物学行为,用Western blot检测脑组织中YAP和TAZ表达,用ELISA法检测脑组织中IL-6、TNF-α、TGF-β1和IL-10水平。将40只C57BL/6老龄小鼠分为control+DMSO组、control+CA3组、model+DMSO组和model+CA3组,每组10只,在造模后7 d,用水迷宫实验检测动物学行为,用ELISA法检测脑组织中炎症因子水平。将60只C57BL/6老龄小鼠分为control+AAV9-Con组、control+AAV9-sh-Iduna、control+AAV9-sh-Iduna+CA3组、model+AAV9-Con组、model+AAV9-sh-Iduna组和model+AAV9-sh-Iduna+CA3组,每组10只,在造模后7 d,用水迷宫实验检测动物学行为,用ELISA法检测脑组织中炎症因子水平。结果:与control比较,model组小鼠脑组织中Iduna的mRNA表达下调(P<0.05)。与model+AAV9-Con组比较,model+AAV9-Iduna组小鼠神经认知障碍显著减轻(P<0.05),脑组织中IL-6和TNF-α表达显著减少(P<0.05),TGF-β1和IL-10表达显著增加(P<0.05),而model+AAV9-sh-Iduna组中的上述情况与model+AAV9-Iduna组相反。Iduna可负向调控Hippo/YAP信号通路相关蛋白YAP和TAZ表达。Hippo/YAP信号通路抑制剂CA3的作用与AAV9-Iduna相似,可抑制PND小鼠围术期神经认知障碍(P<0.05),降低脑组织中IL-6和TNF-α水平(P<0.05)。结论:Iduna通过抑制Hippo/YAP信号通路减轻老龄小鼠PND,降低脑组织中IL-6和TNF-α水平。AIM To investigate the effect of Iduna on inflammatory factors during perioperative neurocognitive disorder(PND)in aged mice,and analyze the role of Hippo/YAP signaling pathway in this process.METHODS Twenty C57BL/6 aged mice were divided into control group and model group(PND mouse model induced by exploratory laparotomy),with 10 mice in each group,and the mRNA level of Iduna in the brain tissue of PND mice was detected by fluorescence quantitative PCR.Before PND modeling,Iduna-overexpressing adeno-associated virus(AAV)vector,sh-Iduna AAV vector and/or Hippo/YAP signaling pathway inhibitor CA3 were injected into the lateral ventricle.C57BL/6 mice were divided into control+AAV9-Con group,control+AAV9-Iduna group,model+AAV9-Con group and model+AAV9-Iduna group,with 10 mice in each group.Seven days after modeling,the zoological behavior was detected by water maze experiment,the expression levels of YAP and TAZ were detected by Western blot,and the levels of IL-6,TNF-α,TGF-β1 and IL-10 in mouse brain tissue were detected by ELISA.Forty C57BL/6 aged mice were divided into control+DMSO group,control+CA3 group,model+DMSO group and model+CA3 group,with 10 mice in each group.Seven days after modeling,the zoological behavior was detected by water maze experiment,and the levels of inflammatory factors in brain tissues were detected by ELISA.Sixty C57BL/6 mice were divided into control+AAV9-Con group,control+AAV9-sh-Iduna,control+AAV9-sh-Iduna+CA3 group,model+AAV9-Con group,model+AAV9-sh-Iduna group and model+AAV9-sh-Iduna+CA3 group,with 10 mice in each group.Seven days after modeling,the zoological behavior was detected by water maze experiment,and the levels of inflammatory factors in brain tissues were detected by ELISA.RESULTS Compared with control group,Iduna was down-regulated in brain tissues of the mice in model group(P<0.05).Compared with model+AAV9-Con group,the neurocognitive impairment of the mice in model+AAV9-Iduna group was significantly alleviated(P<0.05),the expression levels of IL-6 and TNF-αin brain ti

关 键 词：Iduna蛋白 围术期神经认知障碍 炎症 Hippo/YAP信号通路 

分 类 号：R619[医药卫生—外科学] R363.2[医药卫生—临床医学]