七氟醚与芬太尼对老龄大鼠认知功能的影响

摘要

Objective To investigate the effects of sevoflurane and fentanyl on long term cognitive function in aged rats. Methods 120 aged Wistar rats were randomly divided into four groups, rats received sham surgery group, myocardial ischemia reperfusion model group, myocardial ischemia reperfusion model plus sevoflurane group, and myocardial ischemia reperfusion model plus fentanyl group. Blood samples and brain tissue were collected. Hipp-ocampal neurons apoptosis index was calculated using TUNEL assay, and the rate of apoptosis was measured by flow cytometry and intracellular calcium levels in hippocampal neurons. Fluorescent probes were used to determine mitochondrial membrane potential in rat hippocampal neurons. ELISA assay was used to detect the inflammatory factors in the blood. Cognitive function was assessed by Morris water maze test. Results The results demonstrated that treatment of anesthetics shortened the periods of learning and memory incubation, suggesting a protective role in cognitive function. The expression of tumor necrosis factor-α (TNF-α ) and IL-1β decreased, whereas vascular endothelial growth factor(VEGF) expression increased when using anesthetics(P ＜0. 05). In addition, anesthetic treatment reduced neuronal apoptosis rate and apoptosis index, hut improved neuron cytoplasmic and mitochondrial membrane potential activity (P ＜ 0. 05 ). Conclusion Sevoflurane and fentanyl can increase the expression of VEGF and decrease the release of inflammatory factors such as IL-1β and TNF-α. The sevoflurane and fentanyl can also reduce the hippocampus cell apoptosis rate after ischemia-reperfusion in rats, reduce the incidence of cognitive dysfunction in aged rats. Among them, effect of sevoflurane is better.%目的 评价七氟醚与芬太尼对老龄大鼠术后认知功能的影响.方法 随机将120只Wistar老龄大鼠分为4组:假手术组、心肌缺血再灌注模型组、七氟醚组、芬太尼组.术后4周和8周采集大鼠脑组织标本和血标本,流式细胞术用于测定大鼠海马神经元的凋亡率以及胞质内的钙离子水平, TUNEL用于测定大鼠海马神经元细胞凋亡指数.ELISA试验用于测定大鼠心尖血液中炎症因子含量,荧光探针用于测定大鼠海马神经元胞质中线粒体的膜电位情况.采用水迷宫实验检测大鼠术后认知功能.结果 与心肌缺血再灌注模型组相比,七氟醚组和芬太尼组学习潜伏期和记忆潜伏期缩短,肿瘤坏死因子(TNF)-α和白介素(IL)-1β表达降低而血管内皮生长因子(VEGF)表达升高,大鼠神经元凋亡率和凋亡指数降低,钙离子向神经元细胞内的转移减少,神经元胞质内线粒体膜电位活性有所升高(P＜0.05)七氟醚组与芬太尼组相比,其学习潜伏期和记忆潜伏期缩短,TNF-a和IL-1β表达降低而VEGF表达升高,大鼠神经元凋亡率和凋亡指数降低,神经元胞质内线粒体膜电位活性有所升高(P＜0.05).结论 七氟醚和芬太尼可提高老龄大鼠术后 VEGF表达水平,减低IL-1β和TNF-α等炎症因子的释放,七氟醚和芬太尼还能够减少缺血再灌注后大鼠海马神经元细胞的凋亡,减轻了老龄大鼠术后认知功能障碍的发生.其中,七氟醚效果更佳.