血管紧张素Ⅱ-2受体在丙泊酚重复麻醉致新生大鼠海马神经元凋亡中的作用  

Role of angiotensin H type 2 receptor in repeated propofol anesthesia-induced neuroapoptosis in hippocampus of newborn rats

作　　者：张合茂 刘晋敏[1] 李文谦[2] 曾庆繁[2] 

机构地区：[1]贵州医科大学麻醉学院,贵阳市550001 [2]贵州医科大学附属医院麻醉科,贵阳市550004

出　　处：《中华麻醉学杂志》2017年第7期813-816,共4页Chinese Journal of Anesthesiology

基　　金：贵州省科技合作计划项目（TN2014-75）

摘　　要：目的 评价血管紧张素Ⅱ-2受体（AT2R）在丙泊酚重复麻醉致新生大鼠海马神经元凋亡中的作用.方法 7日龄清洁级SD大鼠54只,雌雄不拘,体重10-15 g,采用随机数字表法分为3组（n=18）：对照组（C组）、丙泊酚重复麻醉组（P组）和AT2R激动剂CGP42112A组（G组）.C组腹腔注射0.9％氯化钠注射液3 ml/kg,每20 min给予首次剂量1/2,共5次,连续处理3d;P组腹腔注射丙泊酚30 mg/kg,每20 min给予首次剂量1/2,共5次,连续处理3 d;G组单次腹腔注射CGP42112A 1mg/kg,5 min后腹腔注射丙泊酚30 mg/kg,每20 min给予首次剂量1/2,共5次,连续处理3d.麻醉苏醒2h时,处死6只大鼠取脑组织,采用TUNEL法测定海马神经元凋亡情况,计算神经元凋亡指数;处死6只大鼠分离海马组织,采用Western blot法检测活化的caspase-3、AT2R和过氧化物酶体增殖物激活受体γ（PPARy）的表达;取6只大鼠,于28日龄时采用Morris水迷宫实验测试认知功能.结果 与C组比较,P组逃避潜伏期延长,目标象限停留时间缩短,穿越平台次数减少,海马神经元凋亡指数升高,活化的caspase-3表达上调,AT2R和PPARγ表达下调（P〈0.05）,G组上述指标差异无统计学意义（P〉0.05）;与P组比较,G组逃避潜伏期缩短,目标象限停留时间延长,穿越平台次数增加,海马神经元凋亡指数降低,活化的caspase-3表达下调,AT2R和PPARγ表达上调（P〈0.05）.结论 AT2R活性抑制参与了丙泊酚重复麻醉致新生大鼠海马神经元凋亡.Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor （AT2R） in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups （n=18 each） using a random number table：control group （group C）,repeated propofol anesthesia group （group P） and AT2R agouist CGP42112A group （group G）.In group C,0.9% sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,a single bolus of CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.At 2 h after emergence from anesthesia,6 rats were sacrificed and brains were removed for detection of neuroapoptosis in the hippocampus by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,brains were removed and hippocampi were isolated for determination of the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma （PPARγ） in hippocampal tissues by Western blot.The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγ was down-regulated in group P （P〈0.05）,and no significant change was found in the parameters

关 键 词：受体 血管紧张素 二异丙酚 婴儿 新生 细胞凋亡 海马 神经元 

分 类 号：R726.1[医药卫生—儿科]