【作者】 张金花； 韩威； 高明星； 王旭刚； 胡薛英； 张万坡； 程国富； 刘晓丽； 谷长勤；

【Author】 ZHANG Jin-hua;Han Wei;GAO Ming-xing;Wang Xu-gang;Hu Xue-ying;Zhang Wan-po;Cheng Guo-fu;Liu Xiao-li;Gu Chang-qin;College of Veterinary Medicine, Huazhong Agriculture University;

【机构】 华中农业大学动物医学院；

【摘要】 (目的)探讨雷帕霉素对小鼠乙脑模型中脑部炎症的影响及机制。(方法)180只6周龄BALB/c雌鼠随机分成3组,分别为对照组用DMEM处理;感染组用乙脑病毒(JEV)处理;自噬诱导组用雷帕霉素(Rapa)和乙脑病毒(JEV)处理。组织病理学观察诱导组及感染组小鼠脑组织结构的病理性变化;QPCR检测诱导组及感染组小鼠感染病毒后7d脑部炎症因子的变化;Westernblot检测自噬及炎症相关通路蛋白的变化。(结果)结果显示感染组及诱导组小鼠脑组织出现明显的血管炎性反应及胶质细胞增生,诱导组小鼠脑部血管炎性反应较严重,且持续时间较久。感染组及诱导组小鼠脑组织内炎症因子IL-6、IL-1、TNF-αm RNA水平高于对照组小鼠且差异显著,诱导组小鼠脑组织炎症因子m RNA表达水平高于感染组及对照组且具有显著差异(P<0.05或P<0.01);感染组抑炎因子TGF-βm RNA水平低于对照组小鼠(P<0.05)。Western blot结果显示感染组及诱导组LC3II、PI3K、PAKT、PJNK及P65蛋白表达水平上调,与对照组相比PAKT及P65蛋白上调明显(P<0.05)。结论:雷帕霉素可以通过激活PI3K/AKT信号通路加剧JEV感染小鼠脑部的炎症反应,从而增强对小鼠脑组织的损伤程度。更多还原

【Abstract】 (Objective) To investigate the effect and mechanism of rapamycin on brain inflammation in mouse model of JE.(Methods) One hundred and eighty six-week-old BALB/c female mice were randomly divided into three groups, which were treated with DMEM in the control group; the infected group was treated with JEV; the autophagy-inducing group was treated with rapamycin(Rapa) and JE treatment. Histopathological changes were observed in the brain tissue of the induced and infected mice. QPCR was used to detect changes in brain inflammatory factors in the induced and infected mice 7 days after infection with virus; Western blot was used to detect autophagy and inflammation-related pathway proteins.(Results) The results showed that there were obvious vasculitic reactions and glial cell proliferation in the brain tissue of the infected group and the induced group. The inflammatory reaction of the cerebral vasculature in the induced group was more serious and lasted for a long time. The results of QPCR showed that the levels of IL-6, IL-1 and TNF-α m RNA in the brain of the infected group and the induced group were significantly higher than those in the control group. The expression of inflammatory factor m RNA in the brain of the induced group was higher than that of the infected group. There was significant difference between the control group(P<0.05 or P<0.01). The level of TGF-β m RNA in the infected group was lower than that in the control group(P<0.05). The results of Western blot showed that the expression levels of LC3 II, PI3 K, PAKT, PJNK and P65 were up-regulated in the infected group and the induced group, and the up-regulation of PAKT and P65 protein was obvious.(Conclusion): Rapamycin can aggravate the inflammatory response in the brain of JEV-infected mice by activating PI3 K/AKT signaling pathway, thereby enhancing the damage of brain tissue in mice.更多还原