自噬调节剂对感染日本脑炎病毒小鼠脑部细胞凋亡的影响

旨在研究自噬调控药物对感染日本脑炎病毒（Japanese encephalitis virus，JEV）小鼠脑部细胞凋亡的影响，本试验建立自噬调控药物处理的感染日本脑炎病毒小鼠的动物模型，其中，雷帕霉素为自噬诱导剂，渥漫青霉素及氯喹为自噬抑制剂。实验动物分成8组：DMEM对照组（Control）；JEV感染组（JEV）；JEV+雷帕霉素（Rapamycin）组（JEV+Rapa）；JEV+渥漫青霉素（Wortmannin）组（JEV+Wort）；JEV+氯喹（Chloroquine）组（JEV+CQ）；雷帕霉素组（Rapa）；渥漫青霉素组（Wort）；氯喹组（CQ）。观察不同处理组小鼠的临床症状；透射电镜观察小鼠脑部神经元及胶质细胞的线粒体损伤程度；Tunel染色观察统计小鼠脑部凋亡细胞分布；检测小鼠脑部凋亡因子及凋亡蛋白的表达量。与JEV+Rapa及JEV组相比较，JEV+Wort及JEV+CQ组小鼠出现轻微的神经症状，脑部神经元及胶质细胞线粒体轻度损伤，脑组织较少细胞发生凋亡。不同处理组小鼠脑部凋亡因子及凋亡蛋白的表达量变化差异不显著。综上表明，自噬抑制剂渥漫青霉素和氯喹可以在一定程度上抑制感染日本脑炎病毒小鼠脑组织中细胞凋亡的发生。

Effects of Autophagy Regulators on Apoptosis in the Brain of Mice Infected with Japanese Encephalitis Virus

This experiment was conducted to study the effect of autophagy-regulating drugs on brain cell apoptosis in mice infected with Japanese encephalitis virus(JEV).An animal model was established by treating JEV infected mice with autophagy-regulating drugs.Rapamycin is an autophagy inducer,and wortmannin and chloroquine are autophagy inhibitors.The experimental animals were divided into 8 groups as follows:DMEM control group(Control);JEV infection group(JEV);JEV+rapamycin group(JEV+Rapa);JEV+Wortmannin group(JEV+Wort);JEV+chloroquine group(JEV+CQ);Rapamycin group(Rapa);Wortmannin group(Wort);Chloroquine group(CQ).The clinical symptoms and the degree of mitochondrial damage of neurons and glial cells in the brain of mice were observed.Besides,we examined the distribution of apoptotic cells in the brain of mice and detected the expression of apoptotic factors and apoptotic proteins in the brain of mice.Compared with the JEV+Rapa and JEV groups,the mice in the JEV+Wort and JEV+CQ groups showed mild neurological symptoms,and the mitochondria of neurons and glial cells were mildly damaged,and fewer cells showed apoptosis in the brain.There was no significant difference in the expression of apoptotic factors and apoptotic proteins in the brain of mice in different treatment groups.The results of this study suggested that autophagy inhibitors Wormantin and Chloroquine can partly inhibit the occurrence of apoptosis in the brain tissue of mice infected with JEV.