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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 changes of TNFα expression at different time points after cerebral ischemia-reperfusion in rats with TNFα gene transfection and its effect on microglial activation. Methods: The model of middle cerebral artery occlusion was established by thread occlusion. The expression of TNFα and TNFα mRNA were detected by immunohistochemistry with TNFα and integrin αM (OX42) , 12 h, 24 h, 72 h, 7 d, TNFα expression and microglial activation status. Results: The expression of TNFα was significantly increased at 1 h and 1 h after reperfusion in TNFα transgenic rats at 1 h, and peaked at 12 h and reached the peak at 1 h after reperfusion. The expression of TNFα was still significant, But decreased gradually with the passage of time. At 7 days after reperfusion, TNFα expression was close to that before ischemia. Microglial cells were significantly activated in microglia at 1 h after reperfusion in rat microglia at 1 h after ischemia and reached peak at 1 h after ischemia; reperfusion at 12 h, 24 h, 72 h, At 7 days, microglia in brain tissue was significantly activated compared with non-ischemic brain tissue, but as time went on, microglia activation gradually approached the level of preischemia. CONCLUSION: The dynamic changes of TNFα expression after cerebral ischemia-reperfusion are consistent with the dynamic changes of microglia activation, suggesting that the activation of microglia after cerebral ischemia-reperfusion is mainly related to the overexpression of TNFα.