林正余智曾博尹康

［Gly14］-Humanin减轻大鼠颅脑外伤后氧化应激及细胞凋亡☆

林正*余智△曾博※尹康*

目的 探讨［Gly14］-Humanin（HNG）对大鼠颅脑外伤后脑组织超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）和细胞凋亡的影响。方法 135只SD大鼠分为空白组（n=45）、对照组（n=45）及HNG组（n=45），其中对照组及HNG组建立颅脑外伤模型后前者予右侧股静脉注射生理盐水2 mL/kg，后者则予HNG 2 μL/kg，此后各组每24 h予1次等量生理盐水/HNG，直至大鼠被处死；而空白组不予任何处理。根据处死时间随机分为1 h、3 d和7 d 共3个亚组，每亚组各15只。比较损伤灶周围脑组织MDA、SOD、GSH含量水平及细胞凋亡情况。结果 HNG组大鼠脑组织中MDA含量水平及凋亡细胞计数在损伤后1 h即升高，3 d达到最高值，后开始降低，但7 d时仍高于损伤后1 h水平，均显著低于同一时间点的对照组及空白组（P均＜0.05）；相反，SOD活性在损伤后迅速降低，3 d达到最低值，随后逐渐上升，但7 d时仍低于损伤后1 h水平，均显著高于同一时间点的对照组及空白组（P均＜0.05）；GSH变化规律与SOD基本一致，与各时间点的对照组比较亦有显著性（P均＜0.05）；HNG大鼠脑组织损伤后MDA含量水平与细胞凋亡数呈正相关（r=0.720，P＜0.05），而SOD及GSH的含量与细胞凋亡数呈负相关（r=-0.702，P＜0.05；r=-0.674，P＜0.05）。结论 颅脑外伤后HNG抑制氧化应激反应，进一步减少细胞凋亡，从而发挥神经保护作用。

颅脑损伤 继发性脑损伤 ［Gly14］-Humanin氧化应激 细胞凋亡

【Abstract】Objective To investigate the effects of［Gly14］-Humanin（HNG）on SOD，MDA，GSH and cell apoptosis in a rat model of secondary brain injury.Methods One hundred thirty-five adult and healthy male rats were randomly divided into 3 groups：sham model group（n=45），vehicle control group（n=45）and HNG group（n=45）.Secondary brain injury was induced in the vehicle control and HNG groups using improved Feeney method.Vehicle control received abdominal injections of Sodium Chloride Injection（2 ml/kg）whereas the HNG group received abdominal injections of HNG（2 μL/kg）immediately and 24 h after injury.Each group was divided into three subgroups（n=15 rats per each group）by sacrificed time including 1 h，3 d，and 7 d after injury.The expression levels of SOD，MDA and GSH of the brain tissue were analyzed and the cell apoptosis was examined using TUNEL method after brain contusion.Results MDA and cell apoptosis around the lesion started to increased at 1h，reached a peak at 3d and then gradually subsided but still remained a higher level at 7 d than 1 h.HNG significantly attenuated brain injury-induced increase in MDA and apoptosis at all time points（P＜0.05）.By contrast，SOD started to decrease at 1h，reached the lowest point at 3 d and then gradu-ally recovered but still remained a lower level at 7 d than 1 h.HNG significantly mitigated brain injury-induced increase in MDA and apoptosis at all time points（P＜0.05）.The time course of GSH expression followed a pattern similar to that of MDA.MDA expression was strongly positive correlated with the number of cell apoptosis（r=0.720，P＜0.05），strongly negative correlated with the level of SOD and GSH（r=-0.702，P＜0.05；r=-0.674，P＜0.05）.Conclusions After brain injury，HNG inhibits oxidative stress levels and reduces apoptosis，thereby mitigating secondary brain injury.

【Key words】Traumatic brain injury Secondary brain injury［Gly14］-Humanin Oxidative stress Apoptosis

颅脑损伤（traumatic brain injury，TBI）的发病率呈现持续攀升的趋势［1］，如何阻止颅脑损伤后继发性损伤是研究的热点。颅脑损伤机制十分复杂，其中氧化应激反应在其整个病理生理过程中发挥着枢纽性作用。低分子清除剂（如谷胱甘肽等）、酶清除剂（如超氧化合物歧化酶等）以及脂质过氧化的产物丙二醛（MDA）含量广泛用于衡量氧化应激水平，评估药物抗氧化应激的作用。……