丙泊酚不同麻醉时间对老年大鼠海马CA1区神经元损伤的影响

Effects of propofol anesthesia time on neuron damage in hippocampal CA1 area of aged rats

目的研究丙泊酚不同麻醉时间对老年大鼠海马CA1区神经元损伤及核因子E2相关因子2/抗氧化反应元件(Nrf2/ARE)信号通路的影响.方法将36只大鼠分为对照组(生理盐水)、麻醉2 h组(24 mg·kg^(-1)·h^(-1)的丙泊酚维持麻醉2 h)、麻醉4 h组(24 mg·kg^(-1)·h^(-1)的丙泊酚维持麻醉4 h),每组各12只.麻醉苏醒后,用Morris水迷宫实验检测认知功能.取海马组织,以苏木精-伊红染色检测海马组织病理学改变,比较各组海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平及Nrf2、血红素加氧酶-1(HO-1)蛋白相对表达量.结果对照组、麻醉2h组、麻醉4h组的平均逃避潜伏期分别为(31.50±4.59),(33.12±5.20)和(37.10±4.13)s,穿越平台次数分别为(9.50±1.17),(8.91±1.20)和(5.22±1.05)次,穿越时间分别为(29.21±5.20),(31.58±5.91)和(20.35±4.62)s,SOD分别为(510.62±62.37),(491.26±59.51)和(403.44±52.58)nU·mL^(-1),GSH-Px分别为(161.50±20.35),(152.36±19.51)和(132.09±17.20)nU·mL^(-1).麻醉2h组与对照组大鼠的平均逃避潜伏期、穿越平台次数、穿越时间及海马组织中Nrf2、HO-1蛋白表达量比较,差异均无统计学意义(均P>0.05);麻醉4 h组较对照组的平均逃避潜伏期延长,穿越平台次数减少,平台象限停留时间缩短,海马组织中Nrf2、HO-1蛋白表达量降低(均P<0.05).麻醉2 h组和麻醉4 h组较对照组的海马组织中SOD、GSH-Px水平均降低,且麻醉4 h组低于麻醉2 h组(均P<0.05).结论长时间丙泊酚麻醉可引起老年大鼠海马CA1区神经元损伤及认知功能障碍,其机制可能与Nrf2/ARE信号通路有关.

Objective To investigate the effect of propofol anesthesia time on neuron damage and nuclear factor E2-related factor 2/antioxidant response element(Nrf2/ARE)signaling pathway in hippocampal CA1 area of aged rats.Methods Thirty-six rats were divided into control group(normal saline),2 h anesthesia group(24mg·kg^(-1)·h;propofol maintained anesthesia for 2 h),and 4 h anesthesia group(24 mg·kg^(-1)·h;propofol maintained anesthesia for4 h),12 rats in each group.Morris water maze test was used to detect cognitive function after awakening from anesthesia.The hippocampus was dissected,and the histopathological changes of the hippocampus were detected by hematoxylin-eosin staining.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and the relative expression of Nrf2 and HO-1 protein in the hippocampus of each group were compared.Results The average escape latency of the control group,the anesthesia 2h group,and the anesthesia 4 h group were(31.50±4.59),(33.12±5.20),(37.10±4.13)s,and the times of crossing platforms were(9.50±1.17),(8.91±1.20),(5.22±1.05)times,respectively,the crossing time were(29.21±5.20),(31.58±5.91),(20.35±4.62)s,the SOD were(510.62±62.37),(491.26±59.51),(403.44±52.58)n U·mL^(-1),GSH-Px were(161.50±20.35),(152.36±19.51),(132.09±17.20)n U·mL^(-1).There was no difference in the average escape latency,the number of times of crossing the platform,the crossing time and the expression of Nrf2 and HO-1 protein in the hippocampus between 2 h anesthesia group and control group(all P>0.05).Compared with control group,the average escape latency of the anesthesia 4 h group was prolonged,the number of times of crossing the platform was reduced,the residence time of the platform quadrant was shortened,and the expression of Nrf2 and HO-1 protein in the hippocampus were reduced(all P<0.05).The levels of SOD and GSH-Px in the hippocampus of the anesthesia 2 h group and the anesthesia 4 h group were lower than those of the control group,and the anesthesia 4 h group was lower than the anesthesia 2 h group(all P<0.05).Conclusion Prolonged propofol anesthesia can cause neuronal damage and cognitive dysfunction in the CA1 area of the hippocampus in aged rats,and the mechanism may be related to the Nrf2/ARE signaling pathway.