依达拉奉对内毒素休克大鼠海马细胞凋亡的影响

Effect of edaravone on apoptosis in hippocampal cells in a rat model of endotoxic shock

目的评价依达拉奉对内毒素休克大鼠海马细胞凋亡的影响。方法健康雄性SD大鼠36只，体重200～250g，6周龄，采用随机数字表法，将其分为3组（n=12）：对照组（c组）、内毒素休克组（Es组）和依达拉奉组（E组）。Es组和E组股静脉注射LPS10mg／kg制备大鼠内毒素休克模型，C组给予等容量生理盐水。E组于造模成功后立即静脉注射依达拉奉3mg／kg，每2h注射1次，直至处死；C组和Es组给予等容量生理盐水。每组分别于给予依达拉奉后6、12h时取6只大鼠，取海马，采用硫代巴比妥酸法测定丙二醛（MDA）含量，采用酶联免疫吸附法检测肿瘤坏死因子-α（TNF—α）及白细胞介素-6（IL-6）的含量；采用TUNEL法检测海马CAl区细胞凋亡情况，计算凋亡指数。结果与C组比较，ES组和E组给予依达拉奉后6、12h时海马MDA、TNF—α和IL-6含量升高，给予依达拉奉后12h时凋亡指数升高（P〈0．05）；与Es组比较，E组给予依达拉奉后6、12h时海马MDA、TNF—α和IL-6含量降低，给予依达拉奉后12h时凋亡指数降低（P〈0．05）。结论依达拉奉可减轻内毒素休克大鼠海马细胞凋亡，其机制与降低氧化应激反应及炎性反应有关。

Objective To evaluate the effect of edaravone on apoptosis in hippocampal cells in a rat model of endotoxie shock. Methods Thirty-six male Sprague-Dawley rats, weighing 200-250 g, aged 6 weeks, were randomly divided into 3 groups （n = 12 each） using a random number table： control group （group C） , endotoxic shock group （group ES）, and edaravone group （group E）. Lipopolysaeeharide 10 mg/kg was injected via the femoral vein to establish the model of endotoxic shock in ES and E groups, while the equal volume of normal saline was given in group C. In group E, edaravone 3 mg/kg was intravenously injected immediately after establishment of the model once every 2 h until the animals were sacrificed. The equal volume of normal saline was given instead of edaravone in C and ES groups. At 6 and 12 h after administration of edaravone, 6 rats in each group were sacrificed, and the hippoeampi were isolated for deter- mination of malondialdehyde （MDA） content （using thiobarbituric acid method） , tumor necrosis factor-al- pha （TNF-α） and interleukin-6 （IL-6） contents （using enzyme-linked immunosorbent assay）, and cell apoptosis in hippocampal CA1 region （by TUNEL assay）. The apoptotic index was calculated. Results Compared with group C, the MDA, TNF-α and IL-6 contents were significantly increased at 6 and 12 h after administration of edaravone, and the apoptotic index was increased at 12 h after administration of edaravone in ES and E groups. Compared with group ES, the MDA, TNF-α and IL-6 contents were significantly decreased at 6 and 12 h after administration of edaravone, and the apoptotic index was decreased at 12 h after administration of edaravone in group E. Conclusion Edaravone can reduce apoptosis in hippocampal cells, and the mechanism is associated with the reduced oxidative stress and inflammatory responses in a rat model of endotoxic shock.