丙泊酚对老龄大鼠学习记忆能力的影响及相关机制探讨

Effects of propofol on cognitive function in aged rats and its possible mechanism

目的比较单次注射丙泊酚对老龄大鼠学习记忆能力及麻醉后1、3、7 d大鼠海马内淀粉样前体蛋白(APP)、p-tau、caspase-3和神经元特异性烯醇化酶(NSE)蛋白表达的影响。方法选用18月龄健康雄性SD大鼠,随机分为对照组(C组,n=30)和丙泊酚组(D组,n=30)。D组再按麻醉后1、3、7 d分为D1、D3、D7三个亚组,每个亚组10只大鼠。C组在对应时点,被分为C1、C3、C7三个亚组。D组大鼠经腹腔单次注射丙泊酚60 mg/kg,对应的C组则注射相同容积生理盐水。以Y-型电迷宫测试大鼠的学习记忆能力,蛋白质印迹法测定APP、ptau、caspase-3和NSE蛋白的表达量。结果与C组中对应的亚组比较,D1组大鼠达到学会标准时累计学习的次数显著升高(P<0. 05),D3、D7组大鼠学习的次数与C组差异无统计学意义。与给药前比较,D组大鼠的p-tau、caspase-3蛋白表达量在给药后1、3 d明显增加(P<0. 05),给药后7 d恢复至正常水平; D组各亚组大鼠的APP和NSE蛋白表达水平与给药前比较,差异均无统计学意义。结论丙泊酚单次注射可引起老年大鼠短暂的学习记忆能力受损,原因可能与麻醉后大鼠海马的p-tau、caspase-3蛋白的表达量增加有关。

Objective To study the effects of single dosage of propofol on learning ability and the expression of hippocampal APP,p-tau,caspase-3,and NSE protein in aged rats 1 d,3 d,and 7 d after anesthesia. Methods Sixty male SD rats aged 18 months old,were randomly divided into control group( group C,n = 30) and propofol group( group D,n = 30). Group D was then evenly divided into three sub-groups according to three time points of 1 d( group D1),3 d( group D3),as well as 7 d( group D7) after anesthesia. Group C was also evenly divided into three sub-groups( group C1,group C3,and group C7) according to the corresponding time points. The rats in group D received single dosage of intraperitoneal( i.p.) propofol 60 mg/kg,whereas the rats in group C received equal volume normal saline. Y-maze test was used to observe spatial learning capability 1 d,3 d and 7 d after anesthesia,respectively. After the test,the rats in each sub-group were sacrificed for western blot detection to determine the protein expression of APP,p-tau,caspase-3,and NSE in hippocampus.Results When compared with those in corresponding sub-group of group C,the number of stimulations to reach the learning criteria in group D1 and the protein expression of hippocampal p-tau and caspase-3 in group D1 and group D3 increased significantly( P< 0. 05),and these changes decreased to the baseline level in group D7. Propofol anesthesia did not change the protein expression of hippocampal APP and NSE. Conclusions Single dosage of propofol 60 mg/kg i. p. could damage the spatial learning ability of the 18 months rats,which correlates with the increase of protein expression of p-tau and caspase-3 in hippocampus.