Objective: To explore whether vimentin (VIM) mediates the activation of inflammasome in mice with EV71 infection in the central nervous system.
Methods: Forty VIM knockout mice (VIM-/-, 3 to 5 days old) were randomly divided into control group and infection group. The infection group was intraperitoneally injected with EV71 (108 TCID50), while the control group was injected with PBS (10 µL); another 40 wild-type mice (WT, 3 to 5 days old) were grouped in the same manner. The general conditions of mice were observed each day. Western blotting, ELISA, and RT-PCR were used to measure the levels of IL-1β and casepase-1 in the brain or cerebrospinal fluid. The pathological changes in the cerebella and brain were observed using immunohistochemistry.
Results: Compared with the control group, the VIM-/- mice infected with EV71 showed no significant changes in NLRP3, IL-1β or caspase-1 expression. The WT mice infected with EV71 showed obviously increased NLRP3, IL-1β, and caspase-1 expressions in the central nervous system. The neurons of infected VIM-/- mice exhibited milder cell damage than the those in WT mice.
Conclusion: VIM mediates the activation of inflammasome and promotes brain inflammation and neuronal damage in mice with EV71 infection in the central nervous system.
目的: 观察肠道病毒71型（EV71）感染的小鼠中枢神经系统中波形蛋白（VIM）介导NLRP3炎性小体的活化。
方法: 取3~ 5 d龄的VIM基因敲除型乳鼠（VIM-/-）40只，随机分为EV71感染实验组和空白对照组，20只/组，实验组每只腹腔注射浓度为1×108半数组织培养感染剂量（TCID50）病毒液10 μL，空白组腹腔注射无菌PBS 10 μL，再将同品质的野生型乳鼠（WT）40只以同样方式分组处理。观察小鼠感染状态1周，提取小鼠脑脊液（CSF）和脑组织全蛋白、RNA及组织切片，通过Western blot、ELISA、RT-PCR检测小鼠中枢神经系统的炎症小体激活状况，以及免疫组化技术考察小鼠中枢神经系统的损伤。
结果: 与空白组比较，VIM-/-实验组小鼠在感染EV71后CSF和脑组织中NLRP3炎症小体及其下游产物IL-1β、caspase-1含量无明显变化；而WT实验组小鼠相较VIM-/-型实验组的NLRP3、IL-1β和caspase-1含量显著升高（P < 0.05）；同时WT型实验组IL-1β和caspase-1的mRNA拷贝数亦明显高于VIM-/-型实验组小鼠（P < 0.05）；VIM-/-感染EV71的脑组织神经元受损程度较WT小鼠明显轻微（P < 0.05）。
结论: EV71通过感染小鼠脑组织诱发VIM基因介导的NLRP3炎症小体活化，释放IL-1β和caspase-1，这可能是中枢神经系统炎症和神经元损伤的原因之一。