右美托咪定对肝大部分切除术后小鼠远期认知功能的影响

Effect of dexmedetomidine on long-term cognitive function after partial hepatectomy in mice

目的探讨右美托咪定对肝大部分切除术(PH)后小鼠远期认知功能的影响。方法成年雄性C57BL/6J小鼠40只,采用随机数字表法分为四组,每组10只:对照组(C组)、PH组、生理盐水组(NS组)和Dex组。PH术模型制备后2d,C组和PH组进行Morris水迷宫试验,4次/天,共4d;Dex组小鼠术毕苏醒即刻经腹腔注射Dex 25μg·kg-1·d-1,NS组给予等容量生理盐水,均连续30d后,Dex组和NS组进行Morris水迷宫试验,4次/天,共4d。检测四组小鼠海马组织湿/干重比(W/D)和总含水量(TWC);RT-PCR和Western blot分别检测海马组织caspase-12mRNA及蛋白表达水平;原位末端细胞凋亡检测法(TUNEL法)检测海马组织细胞凋亡指数(AI)。结果与第1天比较,C组、NS组和Dex组小鼠第3、4天逃避潜伏期及游泳距离均明显缩短(P<0.05);与C组比较,PH组小鼠第3、4天逃避潜伏期及游泳距离均明显延长(P<0.05),海马组织W/D、TWC及AI均明显升高(P<0.05),海马组织caspase-12mRNA及蛋白表达水平均明显升高(P<0.05)。与NS组比较,Dex组第3、4天小鼠逃避潜伏期及游泳距离均明显缩短(P<0.05),海马组织W/D、TWC及AI均明显降低(P<0.05),海马组织caspase-12mRNA及蛋白表达水平均明显降低(P<0.05)。结论Dex可改善PH后小鼠远期认知功能,其机制可能与其抑制海马组织caspase-12介导的细胞凋亡有关。

Objective To investigate the effect of dexmedetomidine（Dex）on long-term cognitive function after partial hepatectomy（PH）in mice.Methods Forty adult male C57BL/6Jmice were randomly divided into control group（group C）,group PH,normal saline group（group NS）and group Dex,10 mice per each group.At 2days after PH,the mice of group C and group PH underwent Morris water maze test,four times per day and a total of 4days.The mice were euthanized and hippocampi tissue was immediately excised for determination of wet hippocampi weight to dry hippocampi weight（W/D）and total hippocampi water content（TWC）.The expression levels of cycteinyl aspirate-specific protease 12（caspase-12）mRNA and protein of hippocampi tissue were detected respectively by reverse transcription-polymerase chain reaction（RT-PCR）and Western blot.Apoptosis index（AI）of hippocampi tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）assay.After the mice regained consciousness after operation,animals received intraperitoneally Dex at a dose of 25μg·kg^-1·d^-1 for 30 consecutive days in group Dex.Animals of group NS were given intraperitoneally with the same volume of normal saline.After treatment for 30 consecutive days,the mice of group Dex and group NS underwent Morris water maze test,four times per day and a total of 4days.The mice were euthanized and hippocampi tissue was immediately excised for determination of W/D and TWC.The expression levels of caspase-12 mRNA and protein of hippocampi tissue were detected respectively by RT-PCR and Western blot.AI of hippocampi tissue was determined by TUNEL assay.Results Compared with the first day,the escape latency at the third day,the fourth day and swimming distance were shortened in groups C,NS and Dex（P〈0.05）;Compared with group C,the escape latency at the third day,the fourth day and swimming distance were prolonged（P〈0.05）,W/D,TWC and AI were higher（P〈0.05）,and the expression levels of caspase-12 mRNA and protein of hippocampi tissue were significantly higher（P〈0.05）in group PH.Compared with group NS,the escape latency at the third day,the fourth day and swimming distance were shortened（P〈0.05）,W/D,TWC and AI were lower（P〈0.05）and the expression levels of caspase-12 mRNA and protein of hippocampi tissue were significantly lower（P〈0.05）in group Dex.Conclusion The treatment of Dex could improve the long-term cognitive function after PH in mice,and the mechanism may be to lighten apoptosis mediated by caspase-12 in hippocampi tissue.