丙酮酸乙酯对脾切除术后老龄大鼠认知功能的影响

Impact of ethyl pyruvate on the cognitive function after splenectomy in aged rats

目的探讨丙酮酸乙酯(ethyl pyruvate,EP)对脾切除术后老龄大鼠认知功能的影响。方法健康雄性SD大鼠84只,18月龄,体重500~600g,采用随机数字表法将其分为四组,每组21只:对照组(C组)、手术组(S组)、EP溶液组(E组)和溶剂组(R组)。S组、E组和R组行脾切除术,E组腹腔注射EP 40mg/kg,R组腹腔注射等量EP溶液的溶剂,S组和C组腹腔注射等量生理盐水。于术前5d、术后1、3、7d进行Morris水迷宫实验,记录大鼠逃避潜伏期和游泳距离,水迷宫实验结束后处死大鼠,采用Western blot和RT-PCR法检测四组大鼠海马高迁移率族蛋白1(high mobility group box 1,HMGB1)及晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)的蛋白含量和mRNA表达量。结果与C组比较,术后1、3dS组、E组和R组逃避潜伏期和游泳距离明显延长,海马HMGB1、RAGE蛋白含量和mRNA表达量明显增加(P<0.05)。与S组比较,术后1、3dE组逃避潜伏期和游泳距离明显缩短,海马HMGB1、RAGE蛋白含量和mRNA表达量明显减少(P<0.05)。与术前比较,术后1、3dS组、E组和R组逃避潜伏期和游泳距离明显延长(P<0.05)。结论丙酮酸乙酯可能通过下调海马HMGB1及RAGE的表达改善认知功能。

Objective To investigate the impact of ethyl pyruvate （EP） on cognitive function and the expression of high mobility group box 1 （HMGB1） and receptor for advanced glycation end products （RAGE） after splenectomy in aged rats.Methods Eighty-four male aged Sprague-Dawley rats, 18 months old, weighing 500-600 g, were randomly divided into 4 groups （n=21 each） by random number table method： control group （group C）, surgery group （group S） ethyl pyruvate group （group E） and solution without EP group （group R）.Morris water maze test was performed to evaluate cognitive function 5 days before surgery and 1, 3, 7 days after surgery.Group E was injected with EP 40 mg/kg intrapertoneally after splenectomy, group S and group C were injected with equivalent normal saline after splenectomy, group R was injected with equivalent solution without EP.Rats were killed after Morris water maze test, and the expression of HMGB1 and RAGE protein and mRNA in hippocampus were measured by Western blot and RT-PCR methods.Results Compared with group C, the escape latency and swimming distance were significantly prolonged in groups S, E and R 1 and 3 days after surgery, as well as the expression of HMGB1 and RAGE in hippocampus were significantly up-regulated （P〈0.05）.Compared with group S, the escape latency and swimming distance were significantly decreased and the expression of HMGB1 and RAGE were down-regulated in group E 1 and 3 days after surgery （P〈0.05）.Compared with the preoperative group, the escape latency and swimming distance were significantly prolonged in groups S, E and R 1 and 3 days after surgery （P〈0.05）.Conclusion EP may improve cognitive function in aged rats by down regulating the expression of HMGB1 and RAGE in the hippocampus.