【摘要】 目的 研究柴胡皂苷a(SSa)对癫痫大鼠的神经保护及对海马神经元兴奋性的影响及其作用机制。方法 用氯化锂-匹鲁卡品建立大鼠癫痫模型，将大鼠随机分为模型组、丙戊酸钠(VPA)组、SSa高剂量组和SSa低剂量组，另设15只未造模大鼠作为正常组，每组15只。连续给药4周，Morris水迷宫测试大鼠的学习记忆能力，全细胞膜片钳技术分析海马区神经元的动作电位变化，HE染色观察海马区神经元病变，试剂盒检测大鼠海马组织一氧化氮合酶(NOS)活力及一氧化氮(NO)和环磷酸鸟苷(cGMP)含量，Western blot法检测B淋巴细胞瘤-2(Bcl2)、Bcl-2相关X蛋白(Bax)、Caspase-3和蛋白激酶G(PKG)蛋白表达水平。结果 与正常组比较，模型组大鼠Racine评分显著升高，逃避潜伏期显著延长，60 s内穿越过平台的次数和平台象限的停留时间减少，海马神经元兴奋性显著提高，海马区神经元有明显损伤，海马组织NOS活力、NO和cGMP含量及Bcl2、PKG蛋白表达降低，Bax、Caspase-3增加(P<0.05)。与模型组比较，SSa各剂量组大鼠Racine评分降低，逃避潜伏期缩短，60 s内穿越过平台的次数和平台象限的停留时间增加，海马神经元兴奋性降低，海马区神经元损伤减轻，海马组织NOS活力、NO和cGMP含量及Bcl2、PKG蛋白表达增加，Bax、Caspase-3降低(P<0.05)。结论 SSa对癫痫大鼠具有神经保护作用，并可降低海马神经元的兴奋性，其机制可能与促进NO生成并激活cGMP/PKG通路有关。更多还原

【Abstract】 Objective To study the effect of saikosaponin a(SSa) on the neuroprotection of epileptic rats and the effect on the excitability of hippocampal neurons, and its mechanism of action.Methods Lithium chloride-pilocarpine was used to establish rat epilepsy model. The rats were randomly divided into model group, sodium valproate(VPA) group, SSa high-dose group, and SSa low-dose group. Another 15 unmodeled rats were set as normal group, with 15 rats in each group. After 4 weeks of continuous administration, Morris water maze was used to test the learning and memory ability of rats. Whole cell patch clamp technique was used to analyze the action potential changes of neurons in the hippocampus. HE staining was used to observe the neuronal lesions in the hippocampus. The kits were used to detect the activity of nitric oxide synthase(NOS) and the content of nitric oxide(NO) and cyclic guanosine monophosphate(cGMP) in the hippocampus. Western blot was used to detect the expression levels of B-cell lymphoma-2(Bcl2), Bcl-2-associated X protein gene(Bax), Caspase-3 and protein kinases(PKG) protein. Results Compared with normal group, the Racine score of model group was significantly increased, the escape latency was significantly prolonged, the number of crossing the platform and the residence time in the platform quadrant were reduced within 60 seconds, the excitability of hippocampal neurons was significantly increased, the neurons in the hippocampal region were significantly damaged, the NOS activity, NO and cGMP contents, Bcl2 and PKG protein expression in hippocampus decreased, while the Bax and Caspase-3 protein expression increased(P<0.05). Compared with model group, the Racine scores of rats in each dose group of SSa were decreased, the escape latency was shortened, the number of crossing the platform within 60 seconds and the residence time of the platform quadrant increased, the excitability of hippocampal neurons was reduced, the damage of hippocampus neurons was reduced, the NOS activity, NO and cGMP content, Bcl2 and PKG protein expression in hippocampus increased, but the Bax and Caspase-3 protein expression decreased(P<0.05).Conclusion SSa has a neuroprotective effect on epileptic rats and can reduce the excitability of hippocampal neurons. The mechanism may be related to the promotion of NO production and activation of cGMP/PKG pathway.更多还原