丁苯酞对癫痫大鼠海马组织氧化应激及Nrf2/HO-1信号通路的影响

The effects of DL-3-n-butylphthalide on oxidative stress and Nrf2/HO-1 signaling pathway in hippocampus of status epilepticus rats

目的 探讨丁苯酞(NBP)对匹罗卡品(PILO)致痫大鼠的神经保护作用并对其机制进行研究。方法 将48只SD大鼠随机分为正常组(CON)、癫痫组(SE)、癫痫+NBP60mg·kg^(-1)组(SE+NBP_(60))和癫痫+NBP120 mg·kg^(-1)组(SE+NBP_(120))。NBP中、高剂量组每天分别给予60 mg·kg^(-1)、120 mg·kg^(-1)NBP灌胃连续7d后,用PILO制备癫痫大鼠SE模型,观察各组大鼠大发作潜伏期、SE发生率,ELISA法检测各组大鼠海马氧化应激蛋白水平,Western blot方法检测各组大鼠海马Nrf2、HO-1蛋白表达。结果NBP可延长癫痫大鼠SE潜伏期、降低SE发生率,降低高表达MDA水平,增加SOD活性、GSH蛋白含量,抑制氧化应激。此外,NBP增加癫痫大鼠海马nNrf2、HO-1蛋白表达,增强抗氧化能力。结论 NBP对PILO诱导的急性癫痫发作有明确的保护作用,且有明确量效关系,其作用机制可能与抗氧化及激活Nrf2/HO-1信号通路有关。

Objective To explore the neuroprotective effect of DL-3-n-butylphthalide(NBP) on(pilocarpine,PILO) induced status epilepticus(SE) rats and its mechanism.Methods 48 SD rats were randomly divided into four groups:control group,SE group,SE+NBP_(60)(NBP 60 mg·kg^(-1)) group and SE+NBP_(120)(NBP 120 mg·kg^(-1)) group.After SE+NBP_(60) and SE+NBP_(120) groups were given the corresponding dose of NBP(60 mg·kg^(-1) and 120 mg·kg^(-1),respectively) by gavage for 7 consecutive days,the SE model of epileptic rats was established by PILO,and the SE latency and SE incidence of rats in each group were observed.Oxidative stress level in hippocampus of rats in each group was detected by ELISA.Western blot was used to detect Nrf2 and HO-1 protein expression in hippocampus of rats.Results NBP can prolong the latency of SE,decrease the incidence of SE,decrease the level of MDA,increase the activity of SOD and the content of GSH,and inhibit oxidative stress in SE rats.In addition,NBP increased the expression of nNrf2 and HO-1 proteins in hippocampus of SE rats,and enhanced antioxidant capacity.Conclusion NBP has a significant effect on PILO-induced SE,and there is a clear dose-effect relationship.The mechanism of action may be related to antioxidant and activation of Nrf2/HO-1 signaling pathway.