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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、1h2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12h以内降低(P<0.05),在3d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。
Objective To investigate the effect of FK506 on nitric oxide (NO), nitric oxide synthase (NOS), malondialdehyde (MDA) and superoxide dismutase (SOD) in hippocampus of rats with status epilepticus (SE) (SOD) and its neuroprotective effects. Methods 162 Wistar rats were randomly divided into epilepsy group, FK506 intervention group and control group of 54 rats. SE model was established by intraperitoneal injection of pilocarpine. FK506 group was intraperitoneally injected with FK506 24 h and 1 h prior to injection of pilocarpine, and the control group was injected with equal volume of normal saline. The contents of nitric oxide (NO) in hippocampus , The content of MDA, the activity of NOS and SOD. The expression of neuronal nitric oxide synthase (nNOS) in hippocampus was detected by immunohistochemical method. The morphological changes of neurons were observed by HE staining. Results Compared with epilepsy group, NO, MDA content and NOS activity were significantly decreased in FK506 intervention group (all P <0.01), SOD activity decreased within 12 hours after seizure onset (P <0.05) ). The expression of nNOS in hippocampus decreased (P <0.01), and the number of surviving neurons increased. Conclusion FK506 may play an antiepileptic and brain protective role by inhibiting NOS / NO pathway.