米诺环素对癫痫大鼠海马小胶质细胞的抑制作用

Inhibition effect of Minocycline on hippocampal microglia in epileptic rats

目的探讨米诺环素对癫痫大鼠海马小胶质细胞的抑制作用。方法将40只雄性SD大鼠按随机数字表法分为4组：生理盐水组、青霉素组、米诺环素治疗组和米诺环素预处理组．每组各10只。大鼠腹腔注射青霉素G740万～760万单位／kg以建立大鼠癫痫模型。免疫荧光组织化学技术检测大鼠造模后第1、3天海马小胶质细胞免疫反应性，Westemblotting检测海马肿瘤生长因子-α（TNF—α）蛋白表达情况。结果（1）癫痫发作可激活小胶质细胞。与青霉素组比较，大鼠癫痫发作后第1、3天米诺环素治疗组、米诺环素预处理组海马小胶质细胞活化、增生受抑制，差异均有统计学意义（P〈0．05），且米诺环素预处理组抑制性更突出。（2）大鼠癫痫发作后第1、3天青霉素组、米诺环素治疗组、米诺环素预处理组TNF-α蛋白表达水平明显高于生理盐水组，差异均有统计学意义（P〈0．05）；与青霉素组比较，米诺环素治疗组、米诺环素预处理组TNF-α．蛋白表达水平降低，差异均有统计学意义（P〈0．05），且以米诺环素预处理组更明显。结论米诺环素可有效抑制癫痫大鼠海马小胶质细胞活化、增生和炎症因子TNF-α的释放。

Objective To investigate the inhibition effect of Minocycline on hippocampal microglia in epileptic rats. Methods Forty male SD rats were equally randomized into normal saline control group （NS）, penicillin inducement group, Minocycline post-treatment group and Minocycline pre-treatment group （n=10）. Rat epilepsy models in the later 3 groups were induced by intraperitoneal injection of penicillin G at a dosage of 740 million to 7.6 million units/kg. The level of hippocampal microglia in rats of the 4 groups on the 1^st and 3^rd of inducement was detected by immunofluorescence and the tumor growth factor-α （TNF-α） protein level was detected by Western blotting on the 1^st and 3^rd of inducement. Results Seizure could activate microglia. As compared with those in rats of the penicillin inducement group, the activation and hyperplasia of microglia in the hippocampus in rats of the minocycline post- and pre-treatment groups were obviously inhibited on the 1^st and 3^rd of inducement （P〈0.05）, and the effects were much obvious in the pretreatment group. The level of TNF-α protein in the penicillin inducement group, minocycline post- and pre-treatment groups was significantly higher than that in the NS group on the 1^st and 3^rd of inducement （P〈0.05）; as compared with that in the penicillin inducement group, the level of TNF-α protein in the minocycline post- and pre-treatment groups decreased significantly on the 1^st and 3^rd of inducement （P〈0.05）, especially that in the pretreatment group. Conclusion Minocycline can effectively inhibit the activation and hyperplasia of hippocampal microglia and the releasing of inflammatory factor TNF-α in epileptic rats.