FK506在颅脑损伤中作用的实验研究

Experimental study of Effect of FK506 on Cerebral Injury Secomdary to Craniocerebral Trauma

目的研究创伤性脑损伤(TBI)后,FK506对血浆一氧化氮合酶(NOS)、一氧化氮(NO)、脑组织炎症介质、自由基生成、兴奋性氨基酸(EAAs)水平的影响。方法雄性SD大鼠采用液压损伤法制备脑损伤模型,随机分为损伤组、治疗组和对照组。治疗组于伤后5min开始,一次性腹腔注射FK506(3mg/kg)。伤后30min、6h、24h测量血浆NO、NOS和伤灶及周围脑组织的白介素-6(IL-6)、肿瘤坏死因子α(TNFα)、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、兴奋性氨基酸(EAAs)水平。结果与损伤组相比,治疗组中NOS活性和NO水平显著降低,IL-6、TNFα完全被清除,SOD损耗减少,MPO活性减低,伤后30min组EAAs释放明显减少。结论FK506能抑制伤后NO升高,减少EAAs释放,清除炎症介质,减少自由基生成,对减轻TBI后继发性脑损伤有较大应用价值。

Objective To investigate the effect of FK506 on plasm levels of nitric oxide synthase (NOS) and nitrogen monoxide (NO), and cerebral tissue inflammatory mediums, free radicals and excitatory amino acids(EAAs) contents following craniocerebral trauma (CCT) in rats. Methods CCT was made by fluid percussion device in 84 male SD rats, who were randomly divided into groups of injury, treatment and control. FK506 (3 mg/kg body weight) was intraperitoneally injected 5 minutes after CCT in the treatment group. The rats were killed respectively 30 minutes, 6 hours and 24 hours after CCT. Results The plasma NOS and NO levels, and inflammatory mediums, free radicals and EAAs in the cerebral tissue were determined. The plasma NOS activity and the NO levels, and EAAs in the cerebral tissue descended significantly in the treatment group compared with the injury group. The IL-6 and TNFα in the cerebral tissue of the treatment group where the SOD level was higher and MPO activity was lower than those in the injury group were cleaned completely. Conclusions The present results suggest that FK506 can inhibit NO from ascending and reduce the release of EAAs and clean inflammatory mediums. It is of great value for relieving secondary injury after CCT.