摘要目的 评价七氟醚麻醉对创伤性脑损伤大鼠认知功能障碍的影响.方法 健康雄性Wistar大鼠120只,2～3月龄,体重190～220 g,采用随机数字表法分为4组(n=30):对照组(C组)、创伤性脑损伤组(T组)、七氟醚麻醉组(S组)和创伤性脑损伤+七氟醚麻醉组(T+S组).T和T+S组使用40 g重锤自20 cm高处自由落下撞击大鼠左顶骨窗的方法制备创伤性脑损伤模型.12 d后S组和T+S组吸入3％七氟醚3h;C和T组吸入纯氧3h.分别于麻醉前1d和麻醉后3、7d时,每组随机取10只大鼠行Morris水迷宫实验.水迷宫实验结束后处死大鼠,取海马组织,采用流式细胞术测定海马神经元凋亡率和胞浆钙离子浓度,采用免疫组化法检测葡萄糖调节蛋白78(GRP78)和CAAT增强子结合蛋白同源蛋白(CHOP)的表达水平,采用Western blot法测定caspase-3和caspase-12的表达水平.结果 与C组比较,S组、T组和T+S组逃避潜伏期延长,穿越平台次数减少,海马神经元凋亡率和胞浆钙离子浓度增加,海马组织caspase-3、caspase-12、CRP78和CHOP的表达上调(P<0.05);与T和S组比较,T+S组逃避潜伏期延长,穿越平台次数减少,海马神经元凋亡率和胞浆钙离子浓度增加,海马组织caspase-3、caspase-12、CRP78和CHOP的表达上调(P<0.05).结论 七氟醚麻醉可加重创伤性脑损伤大鼠认知功能障碍,其机制可能与加重内质网应激致钙超载的程度,增加海马神经元凋亡率有关.

abstractsObjective To evaluate the effect of sevoflurane anesthesia on cognitive impairment in rats with traumatic brain injury. Methods One hundred and and twenty healthy male Wistar rats, aged 2-3 months, weighing 190-220 g, were assigned into 4 groups ( n=30 each) using a random number table method: control group ( group C) , traumatic brain injury group ( group T) , sevoflurane anesthesia group ( group S) , and traumatic brain injury plus sevoflurane anesthesia group ( group T+S) . A 40 g hammer was freely dropped onto the left parietal bone window from a height of 20 cm to establish the traumatic brain inju-ry model in T and T+S groups. Twelve days later, S and T+S groups inhaled 3％ sevoflurane for 3 h, and C and T groups inhaled pure oxygen for 3 h. On 1 day before anesthesia and 3 and 7 days after anesthesia, 10 rats in each group were randomly selected for performing Morris water maze test. Rats were sacrificed af-ter the end of Morris water maze test, and the hippocampal tissues were obtained for determination of the apoptosis rate of hippocampal neurons, cytoplasmic calcium concentration [Ca2+]i (by flow cytometry), expression of glucose-regulated protein 78 ( GRP78) and CCAAT∕enhancer-binding protein homologous pro-tein ( CHOP ) ( by immunohistochemistry ) , and expression of caspase-3 and caspase-12 ( by Western blot) . Results Compared with group C, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in S, T and T+S groups ( P<0. 05) . Compared with T and S groups, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in group T+S ( P<0. 05 ) . Conclusion Sevoflurane anesthesia can accentuate cognitive impairment in rats with traumatic brain injury, and the mechanism may be related to aggravating the degree of endoplasmic reticulum stress-induced calcium overload and increasing the apoptosis rate of hip-pocampal neurons.