【摘要】 目的 探究二十二碳六烯酸（DHA）在戊四氮（PTZ）诱导的癫痫模型小鼠的治疗作用及机制。方法 昆明小鼠腹腔注射PTZ构建模型，成功构建模型的小鼠分为模型组、阳性对照组和低、高剂量实验组，各10只；另取10只正常小鼠作为正常组。低、高剂量实验组腹部注射0.10%和0.60%DHA,正常组、模型组均腹部注射等体积生理盐水，阳性对照组腹部注射甘草多糖溶液50 mg·kg^-1。观察病理组织，评估认知学习能力，以酶联免疫吸附测定（ELISA）法检测炎症反应指标，观察惊厥持续时间、发作次数，采用TdT介导的dUTP缺口末端标记法（TUNEL）染色观察脑组织神经元凋亡，采用蛋白质印迹法检测Toll样受体4（TLR4）、髓样分化因子（MyD88）蛋白表达。结果 正常组、模型组、阳性对照组和低、高剂量实验组的逃避潜伏期分别为（12.08±2.13）、（47.82±4.71）、（33.89±3.94）、（28.75±3.51）和（23.16±3.10）s;穿越平台次数为（6.91±0.68）、（3.02±0.35）、（4.25±0.43）、（4.98±0.46）和（5.26±0.53）次；凋亡指数为（4.10±1.02）%、（42.05±3.64）%、（34.05±2.96）%、（26.10±2.15）%和（19.81±1.94）%;TLR4相对表达量为1.00±0.01、1.95±0.10、1.59±0.08、1.38±0.05和1.21±0.03;MyD88相对表达量为1.00±0.01、1.87±0.11、1.62±0.09、1.45±0.07和1.23±0.04。模型组上述指标与正常组、阳性对照组和低、高剂量实验组比较，差异均有统计学意义（均P<0.05）。结论 DHA可改善PTZ诱导的癫痫模型小鼠的认知功能，降低神经元凋亡率，其作用机制可能与TLR4/MyD88信号通路有关。更多还原

【Abstract】 Objective To explore the role of docosahexaenoic acid（DHA） in the inflammatory response and neuronal apoptosis induced by pentylenetetrazole （PTZ） in epilepsy model mice.Methods Kunming mice were intraperitoneally injected with PTZ to construct the model,and the model was successfully constructed.Model mice were divided into model group,positive control group,low and high dose experimental groups,10 mice in each group.Another 10 normal mice were selected as the normal group.Low dose and high dose experimental group were injected with 0.10%and 0.60%DHA,normal group and model group were injected with equal volume of normal saline,and positive control group was injected with 50 mg·kg^-1glycyrrhizol polysaccharide solution.Observe the pathological tissue,evaluate cognitive learning ability,enzyme-linked immunosorbent assay （ELISA） method to detect inflammatory response index,observe the duration of convulsions,attacks,using TdT-mediated dUTP nick end labeling （TUNEL） staining for brain tissue neuronal apoptosis,using immunoblot detection of Toll-like receptor 4 （TLR4）,myeloid differentiation factor（MyD88） expression.Results The escape latency of normal group,model group,positive control group and low dose,high dose experimental group were （12.08±2.13）,（47.82±4.71）,（33.89±3.94）,（28.75±3.51） and（23.16±3.10） s,respectively.The times of crossing the platform were （6.91±0.68）,（3.02±0.35）,（4.25±0.43）,（4.98±0.46） and （5.26±0.53） times.The apoptotic index were （4.10±1.02）%,（42.05±3.64）%,（34.05±2.96）%,（26.10±2.15）%and （19.81±1.94）%;the relative expression levels of TLR4 were 1.00±0.01,1.95±0.10,1.59±0.08,1.38±0.05 and 1.21±0.03.The relative expression levels of MyD88 were 1.00±0.01,1.87±0.11,1.62±0.09,1.45±0.07 and 1.23±0.04.The above indexes in the model group were significantly different from those in the normal group,positive control group,low dose and high dose experimental groups（all P<0.05）.Conclusion DHA can improve the cognitive function of PTZ-induced epilepsy model mice and reduce the rate of neuronal apoptosis,and its mechanism may be related to TLR4/MyD88 signaling pathway.更多还原