目的  探讨上调肿瘤坏死因子α诱导蛋白3(TNFAIP3)的表达对脑缺血再灌注小鼠海马神经元的影响。    方法  C57/BL雄性小鼠36只随机分为 6 组：假手术组(sham)、假手术空载体组(sham-)、假手术TNFAIP3高表达组(sham+)。模型组(model)、模型空载体组(model- )及模型TNFAIP3高表达组(model+ )。采用线栓法制作小鼠大脑中动脉闭塞脑缺血再灌注模型，模型制作成功24 h后海马内注射慢病毒，14 d 后取材，Western blotting 检测 TNFAIP3及ERK信号通路蛋白的表达，2，3，5-三苯基氯化四氮唑（TTC）染色观察缺血面积变化; HE染色观察海马区神经元的形态变化，利用ELISA法检测脂蛋白相关磷脂酶 A2（Lp-PLA2）及白细胞介素（IL）-8 的表达。   结果  Western blotting结果提示，与假手术组比较，模型组TNFAIP3表达显著减少（P<0.05），与模型组比较，模型空载体组TNFAIP3表达无明显变化（P>0.05）,与模型组及模型空载体组比较，模型TNFAIP3高表达组的TNFAIP3表达显著增加（P<0.05）。与假手术组比较，假手术TNFAIP3高表达组TTC染色缺血面积、海马区神经元形态、ERK信号通路蛋白、Lp-PLA2及IL-8的表达无明显变化(P>0.05)；与假手术空载体组及假手术TNFAIP3高表达组比较，模型组TTC染色缺血面积增加，海马区神经元大量损伤，尼氏体数量减少，ERK信号通路蛋白、Lp-PLA2及IL-8的表达显著增加(P＜0.05)；与模型空载体组比较，模型TNFAIP3高表达组 TTC染色缺血面积减小，海马区神经元数量增加，尼氏体数量增多，ERK信号通路蛋白、Lp-PLA2及IL-8的表达显著减少(P＜0.05)。   结论  上调TNFAIP3可能是修复海马神经元脑缺血再灌注损伤的方法之一。

Objective  To investigate the effect of up-regulating tumor necrosis factor alpha induced protein 3 (TNFAIP3) expression on hippocampal neurons in mice with cerebral ischemia-reperfusion.    Methods  The mice were randomly divided into 6 groups: sham group, sham empty vector group (sham-), sham TNFAIP3 high expression group (sham+), model group, model empty vector group (model- ), model TNFAIP3 high expression group (model+ ). A mouse model of middle cerebral artery occlusion and cerebral ischemia-reperfusion was established using the suture method. After the successful establishment of the model, lentivirus was injected into the hippocampus 24 hours later. Two weeks later, samples were collected and Western blotting was used to detect the expressions of TNFAIP3 and ERK signaling pathway proteins. The changes in ischemic area were observed by 2,3,5-triphenyltetrazolium chloride (TTC) staining; HE staining was used to observe the morphological changes of hippocampal neurons, and ELISA was used to detect the expressions of lipoprotein-associated phospholipase A2 (Lp-PLA2) and interleukin (IL)-8.     Results  The results of Western blotting indicated that the TNFAIP3 expression in the model group decreased significantly compared with the sham group (P<0.05); Compared with the model group, there was no significant change in TNFAIP3 expression in the model-  group (P>0.05); The TNFAIP3 expression in the model+  group increased significantly compared with the model group and model-  group(P<0.05). Compared with the sham group, the results of the sham+  group showed that the ischemic area had no significant changes in TTC staining, and there were no significant changes in hippocampal neuronal morphology, and the expressions ERK signaling pathway proteins, Lp-PLA2 and IL-8 (P>0.05); Compared with the sham-  and sham+  groups, the model group showed an increase in ischemic area, significant damage to hippocampal neurons, a decrease in the number of Nissl bodies, and a significant increase in the expressions of ERK signaling pathway proteins, Lp-PLA2, and IL-8 (P<0.05); Compared to the model-  group, the model+  group showed a decrease in ischemic area, an increase in the number of neurons in the hippocampus and the number of Nissl bodies, and a significant decrease in the expressions of ERK signaling pathway proteins, Lp-PLA2, and I-8 (P<0.05).   Conclusion  Up-regulation of TNFAIP3 may be one of the methods for repairing hippocampal neuronal damage caused by cerebral ischemia reperfusion.