FK506对大鼠液压伤后脑保护和相关机理的研究  

The Study of Brain Protection and Its Associate Mechanisms of FK506 Following Fluid Percussion Injury in Rats

作　　者：张桂运[1] 崔尧元[1] 卢亦成[2] 

机构地区：[1]复旦大学附属中山医院神经外科,上海200032 [2]第二军医大学长征医院神经外科,上海200003

出　　处：《中国临床医学》2004年第3期325-327,共3页Chinese Journal of Clinical Medicine

摘　　要：目的 :研究创伤性脑损伤 (TBI)后FK5 0 6短期抗脑水肿的时间剂量效应 ,以及对炎症介质、自由基生成的影响。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Ⅰ、治疗组Ⅱ和对照组。对治疗组按给药时间不同(伤后 5min、30min和 4h) ,分别再分为 3组 ,每 6h腹腔注射一次FK5 0 6 ,连续 4次。所有大鼠伤后 2 4h断头处死。结果 :白介素 - 6 (IL - 6 )、肿瘤坏死因子 -α(TNFα)能被FK5 0 6在不同时相两种剂量下完全抑制 ,伤后 5min给药组在两种剂量下伤侧半球含水量均明显减少 ,健侧半球含水量在各时相两种剂量下均明显减少。与损伤组相比 ,所有治疗组超氧化物歧化酶(SOD)水平均增高 ,但低于对照组 ,而治疗组髓过氧化物酶 (MPO)活性较损伤组明显下降。结论 :按照本实验设计 ,FK5 0 6减少脑水肿的效应具有时相性 ,而其抑制炎症因子 ,减少自由基生成对减轻TBI后继发性损伤有较大价值。Objective: To investigate the effects of FK506 on inflammatory mediums and free radicals and the time- and dose- dependent short-term antiedematous effects of FK506 following traumatic brain injury (TBI). Methods: The male Sprague-Dawley rats were used as the TBI models made by fluid percussion device. The models were randomly divideded into groups of injury, treatmentⅠ, treatmentⅡand control. The treatment groupⅠandⅡwere divided into three groups according to the time (5 minutes,30 minutes or 4 hours after TBI)of administration respectively. FK506 (1 or 3 mg/kg body weight) was administered four-times by intraperitoneal injection every six hours. All rats were killed after twenty-four hours of TBI. Results: IL-6 and TNFα were completely abolished following administration of FK506 at all time points and at both concentrations. The water contents of traumatic hemisphere were significantly reduced in bothⅠandⅡ,which were administered after 5 minutes. The water contents of untraumatic hemisphere were reduced in all treatment groups. Compared to the group of injury, SOD levels were kept higher in all treatment groups but lower than the group of control. The activity of MPO descended obviously in all treatment groups. Conclusion:According to our present design, FK506 has a time-point-limitation in reducing water content of traumatic hemisphere. While its immunosuppressive effects and the ability to reduce free radicals could be of value in attenuating secondary injury after TBI.

关 键 词：FK506 大鼠 脑保护 脑水肿 创伤性脑损伤 炎症介质 

分 类 号：R651.15[医药卫生—外科学]