【摘要】 目的探讨二十二碳六烯酸(DHA)对沙鼠全脑缺血/再灌注诱导的海马神经元凋亡的影响。方法将30只雄性沙鼠随机分为3组:假手术组(S组,n=10)、缺血/再灌注组(I/R组,n=10)和二十二碳六烯酸组(DHA组,130 mg/kg,n=10)。阻断沙鼠双侧颈总动脉造成全脑缺血再灌注模型,DHA组于再灌注即刻给予DHA 130 mg/kg灌胃,连续7天,I/R组和假手术组灌胃给予等量的玉米油。各组分别于7天灌胃结束后采用Mc Grawde五分制评分评价动物行为学变化;通过HE和Nissl染色法检测海马CA1区神经细胞损伤情况。检测海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性及谷胱甘肽(GSH)、丙二醛(MDA)的含量;用蛋白质印迹法检测凋亡相关调控基因Bcl-2、Bax蛋白和ERK信号通路EKR-1/2蛋白的表达变化。结果同I/R组比较,DHA组神经学评分显著降低(P<0.05);HE和Nissl染色结果表明DHA组神经元损伤数量较I/R组明显减少;DHA组与I/R组比较SOD、GSH、GSH-Px活性明显增高,MDA含量显著下降(P<0.05);DHA能拮抗缺血/再灌注引起的Bax、ERK-1/2蛋白表达增多和Bcl-2蛋白表达减少。结论 DHA可减轻全脑缺血/再灌注诱导的神经元损伤,其机制可能与抑制氧化应激反应,激活线粒体途径和抑制ERK信号通路有关。更多还原

【Abstract】 Objective To investigate the effects of DHA on the hippocampal neuronal apoptosis following global cerebral ischemia-reperfusion( I / R) in gerbils. Methods Thirty male gerbils were randomly divided into three groups: sham operation group( group S),ischemia reperfusion group( group I / R) and DHA group( group DHA),with 10 gerbils in each group.Global cerebral I / R was produced by occluding bilateral common carotid arteries for 10 min and then restoring cerebral blood flow. DHA( 130 mg / kg) was given to the gerbils of group DHA by intragastric administration every day. In group S and I / R,gerbils were given the same volume of corn oil. The neurologic deficits score was assessed for neurological symptoms at day 7post-intragastric administration,according to Mc Grawde’s method. Neuronal cell injury of hippocampus CA1 region was assessed by HE and Nissl staining; the activities of SOD,GSH-Px and the content of GSH,MDA were measured. Westernblot was used to observe the expression of Bcl-2,Bax and ERK-1 /2 protein expression in hippocampus CA1 region. Results Compared with group I / R,neurological deficits score was significantly decreased in group DHA( P< 0. 05). Treatment with DHA to ischemic gerbils markedly decreased neurons injury. The activities of SOD,GSH,GSH-Px were increased and the content of MDA was significantly decreased in group DHA( P < 0. 05). DHA inhibited the expression of Bax and ERK and increased the expression of Bcl-2. Conclusion DHA alleviates ischemia / reperfusion induced neuronal impairment which is likely related to the activation of the mitochondrial and inhibition ERK signaling pathway.更多还原