右美托咪定预处理对内毒素血症大鼠海马区Bcl-2、Bax表达及认知功能的影响

Effect of dexmedetomidine pretreatment on hippocampus Bcl-2, Bax expression and cognitive function in endotoxemia rat

目的探讨右美托咪定（dexmedetomidine，Dex）预处理对内毒素血症大鼠海马区凋亡蛋白Bcl-2、Bax的表达及认知功能的影响。方法健康清洁sD雄性大鼠24只，6周龄，体重200～250g，采用随机数字表法将其分为3组（每组8只）：对照组（C组）、内毒素组（E组）和Dex组（D组）。D组腹腔注射Dex 50μg／kg，30min后尾静脉注射脂多糖（lipopolysaccharide，LPS）5mg／kg；E组腹腔注射等容量（2m1）生理盐水，30min后尾静脉注射LPS 5mg／kg；C组腹腔注射等容量生理盐水，30min后尾静脉注射等容量生理盐水。各组于给药后12h，用Morris迷宫测试大鼠认知功能的变化，其后处死大鼠，取大脑海马组织。TUNEL法检测组织凋亡指数（apoptosis index，AI），免疫组织化学法分别检测Bcl-2、Bax蛋白的表达。结果与C组比较，E组和D组潜伏期和游泳总距离增加，穿越平台次数减少（P〈0．05）；与C组比较，E组Bcl-2表达差异无统计学意义（P〉0．05），Bax表达上调，Bcl-2／Bax比值降低（P〈0．05）；D组Bcl-2和Bax表达上调，Bcl-2／Bax比值升高（P〈0．05）。与E组比较，D组AI明显降低，Bcl-2表达上调，Bax表达下调，Bcl-2／Bax升高（P〈0．05）。结论Dex可以改善内毒素血症大鼠的认知功能，其机制可能与调节Bcl-2和Bax蛋白表达，减轻海马区神经元凋亡有关。

Objective To investigate the effects of dexmedetomidine （Dex） pretreatment on endotoxemia rats cognitive function and the expression of Bcl-2 and Bax in hippocampus. Methods A total of twenty4our pathogen-free male SD rats, aged 6 weeks, weighing 200-250 g, were randomly divided into 3 groups（n=8）： control group（group C）, lipopolysaccharide（LPS） group（group E） and Dex group （group D）. Dex 50 μg/kg was injected intraperitoneally and LPS 5 mg/kg was injected via caudal vein 30 rain later in group D. Normal saline 2 ml was injected intraperitoneally and LPS 5 mg/kg was injected via the caudal vein in 30 min later in group E. Normal saline 2 ml was injected intraperitoneally and then injected via the caudal vein 30 min later in group C. After administration of 12 h, the cognitive function of rats were tested by Morris maze, the rats were sacrificed and hippocampal were harvest at each group. Terminal-deoxynucleotidyl transfering mediated nick end labeling was applied to evaluate the apoptosis index （AI）. The expression of protein Bcl-2 and Bax were detected by immunohistochemical method. Results Compared with group C, the latency and swimming distance were increased and numbers of crossing the platform were decreased in group E and D（P〈0.05）, Bcl-2 immunopositivity remains at constantly level in group E （P〉0.05） while Bax immunopositivity was increased. The Bcl-2/Bax ratio was decreased （P〈0.05）, the expression of Bcl-2 and Bax were upregulated in group D, Bcl-2/Bax ratio was increased （P〈0.05）. Compared with group E, the AI index was decreased, Bcl-2 expression was upregulated while Bax expression was downregulated, Bcl-2/Bax ratio was increased in group D（P〈0.05）. Conclusions Dex can improve the cognitive function of rats with endotoxemia. Its mechanism is related to the regulating expression level of Bcl-2 and Bax with a result of decreasing the neuronal apoptosis in hippocampus.