他罗利姆对氯化锂-匹鲁卡品癫痫持续状态炎性因子表达的影响

Effect of tacrolimus on expressions of inflammatory factors during lithium-pilocarpine-induced status epilepticus

目的探索氯化锂-匹鲁卡品癫痫持续状态模型中炎性因子胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)、肿瘤坏死因子α(TNF-α)的表达及他罗利姆(FK506)对其表达的影响。方法随机将健康成年雄性Wistar大鼠168只分为癫痫组、FK506预处理组、对照组。采用HE染色观察癫痫持续状态(SE)后海马神经元的损伤情况,应用实时定量PCR、免疫组织化学染色方法,检测大脑皮层ICAM-1、VCAM-1、TNF-αmRNA及蛋白的表达。结果与对照组比较,癫痫组SE5h TNF-αmRNA表达达到高峰,ICAM-1、VCAM-1 mRNA水平在SE1d出现高峰,SE7d仍增高,FK506预处理则降低其表达。ICAM-1、VCAM-1蛋白在SE1d表达明显升高,FK506预处理则使其表达明显降低,海马神经元损伤明显减轻。结论炎性因子介导的炎症反应在癫痫中可能发挥重要作用,FK506可通过抑制炎症反应发挥抗癫痫和脑保护作用。

Objective To detect expressions of inflammatory factors, ICAM-1, VCAM-1 and TNF-α, in rats after lithium-pilocarpine-induced status epilepticus （SE） and the effect of tacrolimus （FK506） on them. Methods 168 adult male Wistar rats were randomly divided into the SE group, the FK506 group and the control group. The hippocampal neuronal damage after SE was observed by HE staining, and expressions of ICAM-1, VCAM-1 and TNF-ct mRNA and proteins were detected using immunohistochemistry and the real-time quantitative PCR method, respectively. Results Compared with the control group, expression of TNF-α mRNA arrived at a peak 5h after SE. Whereas, ICAM-1 and VCAM-1 mRNA expressions reached maximum levels ld after SE and remained elevated until 7 d after SE. Pre-treatment with FK506 could remarkably decrease mRNA levels of these inflammatory factors. Significant increases in ICAM-1 and VCAM-1 protein expressions were detected at SE ld, which were remarkably attenuated by FK506. FK506 also obviously alleviated hippocampal neuronal damage. Conclusion Inflammatory reaction may play an important role in the pathogenesis of epilepsy. FK506 exerts anti-epileptic and neuroprotective effects through inhibition of inflammatory reaction.