β-arrestin-2通过上调PI3K/Akt信号抑制自噬以减轻小鼠肝脏缺血-再灌注损伤  

β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to alleviate liver ischemia-reperfusion injury in mice

作　　者：王励[1] 谌小龙[1] 刘慧玲[2] 周静[3] 杨逸冬[2] 李慧[1] 陈浩琦 程道柔 吴斌[2] 陈规划[1] 汪根树[1] Wang Li;Chen Xiaolong;Liu Huiling;Zhou Jing;Yang Yidong;Li Hui;Chen Haoqi;Cheng Daorou;Wu Bin;Chen Guihua;Wang Genshu(Department of Hepatic Surgery,Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;不详)

机构地区：[1]中山大学附属第三医院肝脏外科暨肝移植中心,广州510630 [2]中山大学附属第三医院消化内科,广州510630 [3]中山大学附属第三医院病理科,广州510630

出　　处：《器官移植》2020年第6期692-697,共6页Organ Transplantation

基　　金：国家自然科学基金(81170422、81870447);广东省科技计划项目(2017A020215178)。

摘　　要：目的验证β-arrestin-2是否通过上调PI3K/Akt信号抑制自噬对小鼠肝脏缺血-再灌注损伤(IRI)发挥保护作用。方法将C57BL/6背景的β-arrestin-2基因敲除(KO)及野生型(WT)小鼠各12只,随机分为KO小鼠假手术组(KO+sham组),KO小鼠IRI组(KO+IRI组),WT小鼠假手术组(WT+sham组)和WT小鼠IRI组(WT+IRI组),每组各6只。分别建立70%肝脏IRI模型或进行假手术处理,于肝脏再灌注或手术后6 h进行相关研究。采用免疫组织化学(免疫组化)染色检测凋亡信号蛋白裂解半胱氨酸天冬氨酸蛋白酶3(cleaved Caspase-3)、增殖信号蛋白Ki-67及PI3K/Akt通路信号蛋白p-Akt的表达。结果免疫组化染色结果显示,与相应的sham组比较,KO+IRI组和WT+IRI组小鼠肝组织中的cleaved Caspase-3、Ki-67和p-Akt阳性细胞计数均增加(均为P<0.01);与WT+IRI组比较,KO+IRI组小鼠肝组织中cleaved Caspase-3阳性细胞计数增加,Ki-67和p-Akt阳性细胞计数均减少(均为P<0.05)。结论β-arrestin-2可减轻小鼠IRI后肝细胞凋亡、促进其损伤修复,其通过上调PI3K/Akt信号抑制自噬来减轻小鼠肝脏IRI。Objective To verify whetherβ-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to protect the liver from ischemia-reperfusion injury(IRI)in mice.Methods Twelveβ-arrestin-2 knockout(KO)and twelve wild-type(WT)C57BL/6 mice were randomly divided into the KO+sham group,KO+IRI group,WT+sham group and WT+IRI group,six mice in each group.The mouse models with 70%liver IRI were established or sham operation was performed.Relevant experiments were carried out at 6 h after liver reperfusion or operation.The expression levels of apoptosis signal protein cleaved Caspase-3,proliferation signal protein Ki-67 and the PI3K/Akt signal protein p-Akt were detected by immunohistochemical staining.Results Immunohistochemical staining demonstrated that compared with the corresponding sham group,the positive cell count for cleaved Caspase-3,Ki-67 and p-Akt in liver tissues of mice was significantly increased in the KO+IRI and WT+IRI groups(all P<0.01).Compared with the WT+IRI group,the positive cell count for cleaved Caspase-3 in liver tissues of mice was significantly increased,whereas the positive cell count for Ki-67 and p-Akt was significantly decreased in the KO+IRI group(both P<0.05).Conclusionsβ-arrestin-2 can mitigate the liver cell apoptosis and promote the repair of injury after IRI in mice.Moreover,β-arrestin-2 inhibits autophagy by up-regulating the PI3K/Akt signal to alleviate liver IRI in mice.

关 键 词：肝脏 缺血-再灌注损伤 自噬 β-arrestin-2 基因敲除 PI3K/Akt信号 免疫组织化学 

分 类 号：R617[医药卫生—外科学]