摘要
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 m L/kg,后者则予HNG 2μL/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。
ObjectiveTo investigate the effects of [Gly14]-Humanin（HNG） on SOD, MDA, GSH and cell apopto-sis in a rat model of secondary brain injury.MethodsOne hundred thirty-five adult and healthy male rats were random-ly divided into 3 groups： sham model group（n=45）, vehicle control group（n=45） and HNG group（n=45）. Secondarybrain injury was induced in the vehicle control and HNG groups using improved Feeney method. Vehicle control receivedabdominal injections of Sodium Chloride Injection（2 ml/kg） whereas the HNG group received abdominal injections ofHNG（2 μL/kg） immediately and 24 h after injury. Each group was divided into three subgroups（n=15 rats per eachgroup） by sacrificed time including 1 h, 3 d, and 7 d after injury. The expression levels of SOD, MDA and GSH of thebrain tissue were analyzed and the cell apoptosis was examined using TUNEL method after brain contusion.ResultsMDAand cell apoptosis around the lesion started to increased at 1h, reached a peak at 3d and then gradually subsided but stillremained a higher level at 7 d than 1 h. HNG significantly attenuated brain injury-induced increase in MDA and apopto-sis at all time points（P0.05）. 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 increasein MDA and apoptosis at all time points（P0.05）. The time course of GSH expression followed a pattern similar to that ofMDA. MDA expression was strongly positive correlated with the number of cell apoptosis（r=0.720, P0.05）, strongly neg-ative correlated with the level of SOD and GSH（r=-0.702, P0.05; r=-0.674, P0.05）.ConclusionsAfter brain injury,HNG inhibits oxidative stress levels and reduces apoptosis, thereby mitigating secondary brain injury.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2016年第3期180-183,共4页
Chinese Journal of Nervous and Mental Diseases
基金
浙江省医药卫生科技计划项目(编号:201482575)
