抑制MAPK通路对大鼠癫痫持续状态引起海马神经元损伤的保护作用  

Protective effect of inhibiting MAPK pathway on the injured hippocampal neuron induced by status epilepticus in rats

作　　者：聂荔[1] 慕丽娟 王浩[2] NIE Li;LI Xiang;MU Li-juan;WANG Hao(Department of Neurology,Nanshan People＇s Hospital,Shenzhen Guangdong 518052;Department of Neurosurgery,Shenzhen People＇s Hospital,Shenzhen Guangdong 518020,China)

机构地区：[1]广东省深圳市南山区人民医院神经内科,518052 [2]广东省深圳市人民医院神经外科,518020

出　　处：《蚌埠医学院学报》2018年第11期1405-1407,1410,共4页Journal of Bengbu Medical College

摘　　要：目的:探讨抑制MAPK通路对大鼠癫痫持续状态引起海马神经元损伤的保护作用和机制。方法:30只大鼠随机分为对照组、模型组及药物组,用氯化锂-毛果芸香碱制作癫痫持续状态大鼠模型,药物组在氯化锂-毛果芸香碱注射前15 min予腹腔给药SCH58261 0. 05 mg/kg。24 h后观察大鼠海马CA3区的神经元变化及p-38、p-ERK、p-JNK蛋白的表达水平。结果:与模型组大鼠相比,药物组大鼠的痫性发作程度较轻(P <0. 05)。模型组大鼠CA3区可见大量神经元变性和坏死明显,大部分细胞肿胀,体积增大,边缘不清晰,细胞核固缩、碎裂和溶解,细胞脱失明显。与模型组相比,注射SCH58261的药物组大鼠CA3区神经元脱失较少,神经元变性不明显,胞质Nissl小体减少较少。3组大鼠海马区p-JNK、p-p38、p-ERK均有表达,模型组和药物组p-JNK、p-p38、p-ERK均明显高于对照组(P <0. 01),药物组中p-JNK、p-p38表达均明显少于模型组(P <0. 01),p-ERK与模型组差异无统计学意义(P> 0. 05)。结论:大鼠癫痫持续状态会造成海马神经元损伤,而腺苷A2A受体阻断剂SCH58261可通过抑制MAPK通路对海马神经元起一定保护作用。Objective： To investigate the effects of inhibiting MAPK pathway on the injured hippocampal neurons induced by status epilepticus in rats and its mechanism. Methods： Thirty rats were randomly divided into the control group,model group and drug group.The status epilepticus model of rats was established using lithium pilocarpine,and the 0. 05 mg/kg of SCH58261 was intraperitoneally injected into rats in the drug group before 15 minutes of the lithium pilocarpine injection. After 24 hours,the neurons in the hippocampal CA3 region of rats were observed,and the expression levels of p-p38,p-ERK and p-JNK proteins were detected. Results： Compared with the model group,the epileptic seizures degree in drug group was significantly lighter（ P〈0. 05）. A large number of neuron degeneration and necrosis were observed in region in the model group. Most of the cells swelled,the cell volume increased,the cell edge was not clear,the cell nuclei was pyknosis,broken and dissolved,and the cell loss was obvious. Compared with the model group,the neuron loss in CA3 region was less,the degeneration of neurons was not obvious,and the amount of Nissl body decreasing was less in drug group.The expressions of p-JNK,p38 and p-ERK were found in hippocampus of three group,the expressions of p-JNK,p-p38 and p-ERK increased in model group,the expression levels of p-p38 and p-JNK in drug group were less than those in model group（ P〈0. 01）,and the difference of the expression level of p-ERK between the model group and drug group was not statistically significant（ P〉0. 05）.Conclusions： The status epilepticus in rats can lead to the hippocampal neurons damage,and the SCH58261（ adenosine A2 A receptor blocker） can protect the hippocampal neurons by inhibiting the MAPK pathway.

关 键 词：癫痫持续状态 海马 MAPK通路 腺苷A2A受体阻断剂 

分 类 号：R742.1[医药卫生—神经病学与精神病学]