转小鼠TNFα基因大鼠脑缺血时TNFα表达对小胶质细胞激活的影响

The dynamic expression of TNFα and dynamic effects on microglia activation of murine TNFα transgenic rats with cerebral ischemia

目的:观察转小鼠TNFα基因大鼠脑缺血再灌流不同时间TNFα表达的动态变化及其对小胶质细胞激活的影响。方法:采用线栓法制作大鼠大脑中动脉闭塞模型,用TNFα、整合素αM(OX42)免疫组化染色观察转小鼠TNFα基因大鼠未缺血脑组织及缺血1 h再灌注3 h、12 h、24 h、72 h、7d时的TNFα表达及小胶质细胞激活状态。结杲:转小鼠TNFα基因大鼠缺血1 h再灌注3 h TNFα表达较未缺血脑组织明显增加,并达峰值,缺血1 h再灌注12-72 h,TNFα表达仍较显著,但随时间的延长逐渐减少,再灌注7 d时,TNFα表达接近缺血前水平。转小鼠TNFα基因大鼠脑组织小胶质细胞缺血1 h再灌注3 h小胶质细胞极显著地被激活,并达峰值;缺血1 h再灌注12 h、24 h、72 h、7 d时脑组织小胶质细胞与未缺血脑组织比较显著被激活,但随时间的延长,小胶质细胞激活状态逐渐接近缺血前的水平。结论:脑缺血再灌注后TNFα表达的动态变化与小胶质细胞激活的动态变化完全一致,提示脑缺血再灌注后小胶质细胞的激活主要与TNFα的过度表达有关。

Objective: To observe the dynamic expression of tumor necrosis factor α (TNFα) and its effects on microglia activation of murine TNFα transgenic rats with cerebral ischemia. Meth- ods: By suture occlusion technique, the right middle cerebral artery in rat was occluded. Protein expression of TNFα and activation of microglia were examined by immunohistochemistry of TNFα and in-terginaM(OX42). The dynamic expression of TNFα and dynamic effects on microglia activation were observed in murine TNFα transgenic rats subjected to 1 hour occlusion and 3 hours, 12 hours, 24 hours, 72 hours and 7 days reperfusion. Results: TNFa overexpression at 3 hours after reperfusion in the is-chemic brain tissue of murine TNFα transgenic rats was observed and reached the peak. At 12 hours, 24 hours, 72 hours and 7 days reperfusion, TNFα overexpression decreased gradually. Microglia activation at 3 hours after reperfusion in the ischemic brain tissue of murine TNFα transgenic rats was observed and reached the peak. At 12 hours, 24 hours, 72 hours and 7 days reperfusion, microglia activation decreased gradually. Conclusion: The dynamic expression of TNFα accords with dynamic changes of microglia activation of murine TNFα transgenic rats with cerebral ischemia ,this suggests that the microglia activation is strongly related with overexpression of TNFα.