白藜芦醇对新生大鼠七氟烷麻醉后认知功能改变的影响  

Effects of resveratrol on the cognitive function of neonate rats anesthetized by sevoflurane exposure

作　　者：谭宇亭[1] 刘兰[1] 廖芸茜 张攀[1] 徐颖[1] TAN Yu-ting;LIU Lan;LIAO Yun-xi;ZHANG Pan;XU Ying(Department of Anesthesiology,Ministry of Education Key Laboratory of Child Development and Disorders/China National Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Pediatrics/Children＇s Hospital of Chongqing Medical University,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院麻醉科/儿童发育疾病研究教育部重点实验室/儿童发育重大疾病国家科技合作基地/儿科学重庆市重点实验室,重庆400014

出　　处：《解放军医学杂志》2018年第7期600-606,共7页Medical Journal of Chinese People's Liberation Army

摘　　要：目的探讨白藜芦醇(RES)预处理对新生大鼠七氟烷(SEVO)麻醉后认知功能改变的影响。方法将新生6日龄SD大鼠随机分为对照组、RES组、SEVO组和SEVO+RES组。SEVO组及SEVO+RES组采用自制的麻醉箱将大鼠暴露于2.5%七氟烷中,持续3d,每天2h,建立七氟烷暴露模型。将对照组及RES组暴露于除七氟烷以外其余条件相同的环境中,在每次七氟烷暴露前30min分别给予腹腔注射等量安慰剂(0.5%DMSO)或RES(30mg/kg)。于第3天暴露结束后(P8)立即处死,取脑组织,采用HE染色观察脑组织病理形态学变化;RT-PCR检测海马组织中沉默信息调节因子2相关酶1(SIRT1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)及叉头蛋白转录因子3α(FOXO3α)mRNA的表达;Western blotting检测海马组织SIRT1及半胺氨酸蛋白酶3(caspase 3)蛋白的表达;采用分光光度计检测海马组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)含量的变化;第30天(P30)行Morris水迷宫实验评价各组大鼠学习记忆功能。结果与对照组比较,SEVO组神经组织明显疏松、水肿,部分胞质溶解,细胞核固缩、碎裂,SEVO+RES组也可见细胞水肿、核固缩等病理形态,但其程度较SEVO组明显减轻。与对照组比较,SEVO组SIRT1、PGC-1α、FOXO3αmRNA表达均降低(P<0.05),SOD活性降低(P<0.05),MDA水平升高(P<0.05);而与SEVO组相比,SEVO+RES组SIRT1、PGC-1α及FOXO3αmRNA表达明显增强(P<0.05),SOD活性增高(P<0.05),MDA水平降低(P<0.05)。Western blotting结果显示,SEVO组与SEVO+RES组SIRT1表达均低于对照组(P<0.05),SEVO组caspase 3与对照组相比则明显增加(P<0.05);但与SEVO组比较,SEVO+RES组SIRT1表达升高(P<0.05),caspase 3表达降低(P<0.05)。Morris水迷宫实验提示各组大鼠在逃避潜伏期、穿越平台次数以及目标象限停留时间上均无明显差异(P>0.05)。结论 RES可降低氧化应激水平,减轻七氟烷暴露所致新生大鼠脑损伤。但无论是否给予RES预处理,七氟Objective To investigate the effect of pretreatment with resveratrol（RES） on the cognitive function of neonate rats anesthetized by sevoflurane（SEVO） exposure. Methods Newborn SD rats were randomly divided into four groups： control group, RES group, SEVO group, SEVO＋RES group. SD rats were exposed to 2.5% sevoflurane 2 h per day for 3 consecutive days in a self-made anesthesia box to establish a sevoflurane exposure model, and were treated with resveratrol of 30 mg/kg or 0.5% DMSO for 30 min before the sevoflurane anesthesia. Rats were killed at the P8, and the brain tissues were harvested. The morphological changes of brain tissue were observed by HE staining, the expression of SIRT1, PGC-1α and FOXO3α mRNA in hippocampus was detected by RT-PCR, the expression of SIRT1 and caspase 3 protein in hippocampus was detected by Western blotting, and the changes of superoxide dismutase（SOD） and malondialdehyde（MDA） activity in hippocampal homogenate were detected by chemical method of SOD and MDA Kits. The Morris water maze was used to assess the learning and memory function of rats at P30. ResultsCompared with Control group, the nerve tissue of SEVO group was obviously loose, edema, partial cytoplasm dissolution, nuclear pyknosis, and fragmentation. The nerve tissue of SEVO＋RES group also showed cell edema, nuclear pyknosis and other pathological changes in a markedly lighter degree than that in SEVO group. Compared with Control group, the expressions of SIRT1, PGC-1αand FOXO3α mRNA and SOD activity decreased（P〈0.05）, and MDA level increased（P〈0.05） in SEVO group. Compared with SEVO group, the expressions of SIRT1, PGC-1α and FOXO3α mRNA and SOD activity significantly increased（P〈0.05） and MDA level decreased（P〈0.05） in SEVO＋RES group. Western blotting showed that the SIRT1 expressions in SEVO group and SEVO＋RES group were lower than in Control group（P〈0.05）, and the expression of caspase 3 protein in SEVO group significantly increased than in Control group�

关 键 词：白藜芦醇 七氟烷 认知 氧化应激 

分 类 号：R614[医药卫生—麻醉学]