丙泊酚合并低氧通过p38通路损伤未成熟大鼠的认知功能  

Propofol combined with hypoxia induces cognitive dysfunction in immature rats via p38 pathway

作　　者：张敬 于晴 刘阳[4] 刘辉[2,3] 孙茫[3,4] 田芹 涂生芬[1] ZHANG Jing;YU Qing;LIU Yang;LIU Hui;SUN Mang;TIAN Qin;TU Shengfen(Department of Anesthesiolog,Children's Hospital of Chongqing Medical University,Chongqing 400014,China;Hospital of Chongqing Medical University Ministry of Education Key Laboratory of Child Development and Critical Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,China;China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,China;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麻醉科,重庆400014 [2]重庆医科大学附属儿童发育疾病研究教育部重点实验室,重庆400014 [3]重庆医科大学附属儿童发育重大疾病国家国际科技合作基地,重庆400014 [4]重庆医科大学附属儿科学重庆市重点实验室,重庆400014

出　　处：《南方医科大学学报》2018年第11期1294-1299,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(31200853);重庆市自然科学基金(cstc2012jjA10036);重庆市卫计委高端人才后备项目(2015HBRC007);国家临床重点专科建设项目(国卫办医函[2013]544).

摘　　要：目的探讨丙泊酚合并低氧对未成熟大鼠认知功能的影响及与p38通路、tau蛋白的关系。方法将90只7日龄(P7)SD大鼠随机分为丙泊酚低氧组、丙泊酚空气组、丙泊酚氧气组、脂肪乳低氧组、脂肪乳空气组、脂肪乳氧气组。丙泊酚低氧组、丙泊酚空气组、丙泊酚氧气组幼鼠腹腔注释丙泊酚50 mg/kg,脂肪乳低氧组、脂肪乳空气组、脂肪乳氧气组幼鼠腹腔注射脂肪乳5.0 mL/kg,1次/d,连续7 d。每次注射完毕后分别放入氧浓度为18%、21%、50%的暖箱(38℃),待幼鼠翻正反射完全恢复后放回鼠笼。另取90只P7大鼠分为阻滞剂加丙泊酚低氧组、阻滞剂加丙泊酚空气组、阻滞剂加丙泊酚氧气组、阻滞剂加脂肪乳低氧组、阻滞剂加脂肪乳空气组、阻滞剂加脂肪乳氧气组,腹腔注射p-p38阻滞剂15 mg/kg,30 min后分别与丙泊酚低氧组、丙泊酚空气组、丙泊酚氧气组、脂肪乳低氧组、脂肪乳空气组、脂肪乳氧气组进行同样处理。采用Western blot法检测海马组织磷酸化tau蛋白、总tau蛋白、p-p38含量,水迷宫实验评估大鼠空间学习和记忆能力。结果丙泊酚低氧组、丙泊酚空气组与相应脂肪乳组相比p-p38、磷酸化tau蛋白、总tau蛋白含量升高(P<0.05),丙泊酚氧气组、阻滞剂加丙泊酚空气组、阻滞剂加丙泊酚低氧组、阻滞剂加丙泊酚氧气组与相应脂肪乳组相比各蛋白表达无差异(P>0.05)。丙泊酚低氧组、丙泊酚空气组、阻滞剂加丙泊酚空气组、阻滞剂加丙泊酚低氧组与相应脂肪乳组相比潜伏期延长(P<0.05)、穿越平台次数减少、第三象限停留时间缩短(P<0.05);丙泊酚氧气组、阻滞剂加丙泊酚氧气组与相应脂肪乳组相比水迷宫实验结果无差异。阻滞剂加丙泊酚氧气组与丙泊酚氧气组,阻滞剂加丙泊酚低氧组与丙泊酚低氧组、阻滞剂加丙泊酚空气组与丙泊酚空气组之间水迷宫实验结果有差异(P<0.05);脂肪乳低�Objective To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects. Methods Ninety 7-day-old(P7) SD rats were randomized for daily intraperitoneal injection of propofol(50 mg/kg) or lipid emulsion(5.0 mL/kg) for 7 consecutive days.After each injection, the rats were placed in a warm box(38℃) with an oxygen concentration of 18%(hypoxia), 21%(normal air), or 50%(oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker(15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test. Results Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment(P<0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups(P<0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels(P<0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels. Conclusion Propofol combined with hyp

关 键 词：丙泊酚 低氧 P38通路 TAU蛋白 认知障碍 新生大鼠 

分 类 号：R726.1[医药卫生—儿科]