他罗利姆对癫痫持续状态大鼠海马的影响及脑保护作用

目的研究免疫抑制剂他罗利姆（FK506）对癫痫持续状态（SE）大鼠海马组织一氧化氮(NO)、一氧化氮合酶（NOS）、丙二醛（MDA）和超氧化物歧化酶（SOD）的影响及其脑保护作用。方法随机将162只Wistar大鼠分为癫痫组、FK506干预组、对照组各54只。采用匹鲁卡品腹腔注射制作SE模型，FK506干预组在注射匹鲁卡品之前24、1?h 2次腹腔注射FK506，对照组注射等体积生理盐水；采用比色法和羟胺法分别检测海马组织中NO、MDA含量、NOS、SOD活性；采用免疫组化法检测海马组织神经元型一氧化氮合酶（nNOS）的表达；采用HE染色观察神经元形态变化。结果与癫痫组相比，FK506干预组NO、MDA含量、NOS活性明显降低（P均＜0.01），SOD活性在癫痫发作后12?h以内降低（P＜0.05）,在3?d之后升高（P＜0.01）；海马nNOS的表达降低（P＜0.01），存活神经元增加。结论FK506可能通过抑制NOS/NO途径发挥抗癫痫和脑保护作用。

Effect of tacrolimus on protection of neurons in the hippocampus of rats with status epilepticus

Objective To investigate the effect of tacrolimus on expressions of nitric oxide (NO)、 nitric oxide synthase ( NOS), malondialdehyde (MDA) and superoxide dismutase (SOD) and the protection on neurons in the hippocampus of rats with status epilepticus. Method 162 male Wistar rats were randomly divided into the epilepsy group, the tacrolimus group and the control group. The epilepsy group and the tacrolimus group were injected with pilocarpine to establish status epilepticus models. The tacrolimus group was also pre-treated with tacrolimus at 24h and 1h before pilocarpine injection. The control group only received normal saline. The contents of NO, NOS, MDA and SOD of the hippocampus were assayed and expression of neuronal nitric oxide synthase (nNOS) in the hippocampus was determined by immunohistochemical techniques. Results Compared with the epilepsy group, the contents of NO, NOS and MDA and expression of nNOS of the tacrolimus group were obviously decreased (P < 0.01), activity of SOD was decreased in the first 12 h, but increased after 3 d, and the brain injury was less severe. Conclusion The nNOS/NO pathway may underlie one of the potential mechanisms of anti-epileptic and tacrolimus produces a protective effect.