右美托咪定联合舒芬太尼对大鼠认知功能的影响及机制研究

Effects of dexmedetomidine combined with sufentanil on cognitive function in rats and its action mechanism

目的探讨右美托咪定联合舒芬太尼麻醉对大鼠认知功能影响及机制研究。方法将老年健康雄性SD大鼠随机分为对照组、手术组、舒芬太尼组和联合组,每组15只。对照组大鼠正常饲养,联合组大鼠在术前30 min给予舒芬太尼和右美托咪定腹腔注射,舒芬太尼组大鼠在术前30 min给予舒芬太尼以及0.9%氯化钠溶液腹腔注射,手术组大鼠在术前30 min给予等体积0.9%氯化钠溶液腹腔注射,舒芬太尼组以及联合组大鼠进行体外循环手术。比较4组大鼠术后Y迷宫试验观察大鼠神经行为学变化,并检测4组大鼠脑脊液Aβ、p-Tau及PSD95蛋白表达,以及大鼠海马组织caspase-3、bax表达情况。结果术后3、5、7 d,手术组、舒芬太尼组、联合组大鼠Y迷宫试验达标训练次数均显著高于对照组(P<0.05),而联合组大鼠Y迷宫试验达标训练次数显著低于手术组、舒芬太尼组(P<0.05)。术后3、5、7 d手术组、舒芬太尼组、联合组大鼠Y迷宫试验潜伏期显著高于对照组(P<0.05),而联合组大鼠Y迷宫试验潜伏期显著低于手术组、舒芬太尼组(P<0.05)。对照组大鼠脑脊液Aβ、p-Tau蛋白含量显著高于其他3组(P<0.05),其中舒芬太尼组、联合组大鼠脑脊液Aβ、p-Tau蛋白含量显著高于手术组(P<0.05),而联合组大鼠脑脊液Aβ、p-Tau蛋白含量显著高于舒芬太尼组(P<0.05)。手术组、舒芬太尼组以及联合组大鼠海马组织中Casepase-3及Bax蛋白显著高于对照组(P<0.05),联合组大鼠海马组织中Casepase-3及Bax蛋白表达较手术组明显降低(P<0.05)。结论右美托咪定联合舒芬太尼可有效保护体外循环手术大鼠认知功能,其作用机制可能与调节脑脊液Aβ、p-Tau蛋白含量、以及调节海马组织中Casepase-3及Bax蛋白表达有关。

Objective To investigate the effects of dexmedetomidine combined with sufentanil on cognitive function in rats and its action mechanism.Methods Sixty aged healthy male SD rats were randomly divided into control group(n=15),operation group(n=15),sufentanil group(n=15)and combination group(n=15).The rats in control group were fed normally.The rats in operation group were treated with the same volume of 0.9%NaCl injected intraperitoneally at 30minutes before operation.The rats in sufentanil group were treated by intraperitoneal injection with sufentanil and intraperitoneal injection of 0.9%sodium chloride solution at 30minutes before operation.The rats in combination group were treated with sufentanil and intraperitoneal injection of dexmedetomidine at 30minutes before operation.Cardiopulmonary bypass operation was performed on the rats in sufentanil group and combination group.Y labyrinth test was performed to observe the neurobehavioral changes after operation in rats in the three groups.And the expression of Aβ,pTau in cerebrospinal fluid and beta protein as well as the expression of caspase3 and bax in the hippocampus of rats in all groups were detected and compared.Results The standard training frequencies in Y maze test at 3d,5d,7d after operation in operation group,sufentanil group and combination group were significantly higher than those in control group(P<0.05),however,the standard training frequencies in combination group were significantly lower than those in operation group and sufentanil group(P<0.05).The duration of latency by Y maze test at 3 d,5 d,7 d after operation in operation group,sufentanil group and combination group was significantly higher than that in control group(P<0.05),while the duration of latency in combination group was significantly lower than that in operation group and sufentanil group(P<0.05).Moreover,the levels of protein Aβ,pTau in control group,combination group,sufentanil group and operation group were decreased in order(P<0.05).In addition,the expression levels of Casepase-3 and Bax in the hippocampus of rats in combination group,sufentanil group and operation group were significantly higher than those in control group(P<0.05),and the expression levels of Casepase-3 and Bax in combination group were decreased significantly,as compared with those in operation group(P<0.05).Conclusion Dexmedetomidine combined with sulfentanyl can effectively protect the cognitive function of rats who underwent cardiopulmonary bypass surgery,which may be related to the regulation of the content of protein Aβ,pTau and the expression of Casepase-3 and Bax in hippocampus.