槟榔碱对丙泊酚麻醉大鼠术后认知功能及海马GABA表达影响

Effect of arecoline on postoperative cognitive function and hippocampal GABA expression in propofol-anesthetized rats

目的探讨槟榔碱对丙泊酚麻醉大鼠的认知功能及γ-氨基丁酸A(GABA)受体的影响。方法60只SD大鼠分为丙泊酚组、丙泊酚+槟榔碱组、槟榔碱组及对照组,每组15只。丙泊酚组给予1%丙泊酚中/长链脂肪乳6mL/kg,丙泊酚+槟榔碱组给予1%丙泊酚中/长链脂肪乳+槟榔碱2.5 mg(kg·d)灌胃,槟榔碱组给予槟榔碱2.5 mg/(kg·d)灌胃,对照组给予中/长链脂肪乳灌胃。1次/d,持续3 d。进行定位航行及空间探索实验,尼氏体染色,免疫组织化学、Western Blot检测GABA蛋白表达。结果麻醉时间越长,各组大鼠逃逸潜伏期、总里程越短,第5天时是获取丙泊酚致认知障碍模型的最佳时间。丙泊酚组、丙泊酚+槟榔碱组大鼠逃逸潜伏期、总里程均高于对照组,丙泊酚组高于丙泊酚+槟榔碱组,槟榔碱组低于丙泊酚+槟榔碱组,差异均有统计学意义(P均<0.05)。麻醉第5天时,丙泊酚组、丙泊酚+槟榔碱组大鼠穿越平台区域次数、时间低于对照组,丙泊酚组低于丙泊酚+槟榔碱组,槟榔碱组高于丙泊酚+槟榔碱组,差异均有统计学意义(P均<0.05)。对照组、槟榔碱组海马区尼式体分布、排列正常;丙泊酚组尼式体消失,神经细胞数量减少,细胞核破裂、丢失;丙泊酚组+槟榔碱组较对照组神经细胞排列疏松,形态不规则,尼式体减少。对照组、槟榔碱组、丙泊酚+槟榔碱组及丙泊酚组GABA蛋白表达量分别为(0.89±0.12)、(0.87±0.11)、(0.49±0.15)、(0.09±0.01),各组比较差异有统计学意义(P<0.05)。结论槟榔碱可改善丙泊酚诱导的认知功能障碍,可能与增加海马区GABA的表达有关。

Objective To investigate the effect of arecoline on the cognitive function and level ofγ-aminobutyric acid(GABA)in rats with propofol anesthesia.Methods 60 SD rats were divided into propofol group,arecoline group,propofol+arecoline group and control group,each group 15.The rats in the propofol group were given 1%propofol medium/long chain fat milk injection(6 mL/kg).The rats in the arecoline group were given arecoline[2.5 mg/(kg·d)].Arecoline[2.5 mg/(kg·d)]was given to the rats in the propofol+arecoline group after 1%propofol medium/long chain fat milk injection(6 mL/kg)anesthesia.The rats in the control group were given iso-volume medium/long-chain fat milk gavage[2.5mg/(kg·d)],once per day for 3 consecutive days.The space exploration experiment was carried out in the 2nd day after the end of the navigation experiment.HE staining and Neisseria staining were performed after gastric lavage.The expression of GABA protein was detected by immunohistochemistry and Western blot.Results There were differences of escape incubation period and total mileage in groups(P all<0.05).There were differences of crossed the platform area in groups(F=12.96,14.08,P all=0.00).Nissl body distribution in hippocampal area of control group and arecoline group was normal.The Nissl body in the propofol group disappeared,the number of nerve cells decreased,the nucleus was ruptured and lost;the nerve cells in arecoline group and propofol group were more lost than those in the control group;the morphology was irregular,and the Nissl body decreased.There were differences of expression of GABA protein in groups(0.89±0.12),(0.87±0.11),(0.49±0.15),(0.09±0.01)(P all=0.00).Conclusion Arecoline could improve the cognitive impairment induced by propofol,and is associated with enhanced hippocampal GABA level.