巨细胞病毒UL144对SD幼鼠肝细胞损害的分子机制  

The damage of cytomegalovirus UL144 to mouse hepatocytes and its molecular mechanism

作　　者：温正旺[1] 陈益平[1] 任迪索 胡玲珑 石海矾[1] 陈洁[1] Wen Zhengwang;Chen Yiping;Ren Disuo;Hu Linglong;Shi Haifan;Chen Jie(Department of Infectious Diseases,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童感染科,浙江温州325000 [2]温州医科大学仁济学院,浙江温州325000

出　　处：《国际流行病学传染病学杂志》2021年第3期221-225,共5页International Journal of Epidemiology and Infectious Disease

基　　金：温州市科技局课题(Y20180002、Y20180003、Y20190213)。

摘　　要：目的探索巨细胞病毒UL144对SD幼鼠肝细胞损害的影响及其内在分子机制。方法取健康SD幼鼠24只,分成3组,分别为空白组,空载组和UL144组(实验组),空白组不做处理,空载组尾静脉注射空载腺病毒,实验组SD幼鼠尾静脉注射携带有UL144蛋白的慢病毒。RT-PCR法检测各组中UL144 RNA,ELISA法检测caspase-8、caspase-12和Toll样受体(TLR4)表达情况,HE染色检测肝脏细胞的变化,TUNEL法检测SD幼鼠肝细胞的凋亡情况。结果三组幼鼠肝脏内的UL144 RNA、caspase-8和TLR4蛋白的表达量差异有统计学意义(F=156.166、97.287和67.624,P均<0.05),其中实验组的UL144 RNA、caspase-8和TLR4蛋白表达量分别为1.823±0.080、0.305±0.004和0.880±0.068,高于空载组及空白组(P均<0.05)。实验组、空载组和空白组的caspase-12的表达水平分别为0.127±0.005、0.116±0.003和0.104±0.005,差异无统计学意义(F=2.156,P>0.05);肝细胞凋亡指数分别为7.68±0.37、2.26±0.24和2.38±0.16,差异有统计学意义(F=158.427,P<0.05),实验组高于空白组和空载组(P均<0.05)。结论巨细胞病毒UL144可能通过激活TLR4并介导效应分子caspase-8诱导了幼鼠肝脏细胞的凋亡,内质网应激通路caspase-12没有参与。Objective To explore the effect of cytomegalovirus UL144 on mouse hepatocyte damage and its molecular mechanism.Methods A total of 24 healthy SD mice were divided into 3 groups:blank group,empty group and UL144 group(experimental group).Blank group was not treated,empty group was given empty adenovirus by tail vein injection,and the experimental group was given lentivirus carrying UL144 protein by tail vein injection.RT-PCR was used to detect UL144 RNA in each group,and ELISA was used to detect caspase-8,caspase-12 and Toll-like receptor 4(TLR4)expression.The changes of liver cells were detected by HE staining,and the apoptosis of liver cells in mice were detected by TUNEL.Results The UL144 RNA,caspase-8 and TLR4 protein expression in the liver of three groups were significantly different(F=156.166,97.287 and 67.624,P all<0.05).In UL144 group,the expression levels of UL144 RNA,caspase-8 and TLR4 protein were 1.823±0.080,0.305±0.004 and 0.880±0.068,which were significantly higher than those in the empty group and control group(P all<0.05).Among the experimental group,empty group and blank group,there were no statistical differences in the expression levels of caspase-12(0.127±0.005,0.116±0.003 and 0.104±0.005)(F=2.156,P>0.05);and there were statistical differences in the apoptosis index(7.68±0.37,2.26±0.24 and 2.38±0.16)(F=158.427,P<0.05),with experimental group significantly higher than empty group and control group(P all<0.05).Conclusions Cytomegalovirus UL144 may induce the apoptosis of mouse liver cells by activating TLR4 and mediating the effector molecule caspase-8.And the endoplasmic reticulum stress-specific caspase-12 apoptosis way is not involved.

关 键 词：巨细胞病毒 TOLL样受体4 肝细胞 凋亡 

分 类 号：R725.1[医药卫生—儿科]