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  • 刘辉,孙茫,田芹,张敬,陈杭,涂生芬.丙泊酚对未成年肥胖模型大鼠认知功能损害的机制[J].第二军医大学学报,2020,41(6):686-690    [点击复制]
  • LIU Hui,SUN Mang,TIAN Qin,ZHANG Jing,CHEN Hang,TU Sheng-fen.Mechanisms of propofol-caused cognitive impairment in young obese rats[J].Acad J Sec Mil Med Univ,2020,41(6):686-690   [点击复制]
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丙泊酚对未成年肥胖模型大鼠认知功能损害的机制
刘辉1,2,孙茫3,田芹1,张敬1,2,陈杭1,涂生芬1*
0
(1. 重庆医科大学附属儿童医院麻醉科, 重庆 400014;
2. 重庆医科大学附属儿童医院儿科研究所核酸蛋白实验室, 重庆 400014;
3. 重庆医科大学附属儿童医院儿科研究所儿童泌尿生殖发育与组织工程重点实验室, 重庆 400014
*通信作者)
摘要:
目的 研究丙泊酚对未成年肥胖大鼠认知功能的影响,并探讨其与海马组织中血红素加氧酶1(HO-1)、超氧化物歧化酶1(SOD1)蛋白及血浆中S100钙结合蛋白β(S100β)表达的关系。方法 取3周龄雄性SD大鼠140只,随机分为基础饲料组(n=40)和高脂饲料组(n=100)。基础饲料组予基础饲料喂养,高脂饲料组予高脂饲料喂养。喂养4周后,取高脂饲料组体质量≥基础饲料组平均体质量+1.4倍标准差的40只大鼠判定为肥胖建模成功。将基础饲料组大鼠随机分为正常脂肪乳组(NL组)、正常丙泊酚组(NP组),将建模成功的肥胖大鼠随机分为肥胖脂肪乳组(OL组)、肥胖丙泊酚组(OP组),每组均为20只。丙泊酚组腹腔注射丙泊酚100 mg/kg,脂肪乳组(对照)腹腔注射脂肪乳100 mg/kg,每天注射1次,连续7 d。停药后第1天,各组大鼠行Morris水迷宫实验评估大鼠空间学习记忆能力,ELISA检测大鼠血浆S100β含量,蛋白质印迹法检测海马组织中HO-1、SOD1蛋白表达,H-E染色观察海马CA1区神经元的变化。结果 与OL组比较,OP组第1~5天逃逸潜伏期均延长(P均<0.05),第三象限停留时间缩短(P<0.05),穿越平台次数减少(P<0.05),血浆中S100β蛋白表达升高(P<0.05),海马组织中HO-1和SOD1蛋白相对表达量均降低(P均<0.05),海马CA1区神经元数量减少(P<0.01)。与NL组比较,NP组第1、2天逃逸潜伏期均延长(P均<0.05),上述其余指标差异均无统计学意义(P均>0.05)。结论 丙泊酚通过下调未成年肥胖大鼠海马组织中抗氧化因子HO-1和SOD1的表达使大鼠S100β表达和氧化应激增加,从而导致其认知功能损害。
关键词:  丙泊酚|肥胖|抗氧化因子|S100钙结合蛋白β|认知障碍
DOI:10.16781/j.0258-879x.2020.06.0686
投稿时间:2020-02-17修订日期:2020-05-11
基金项目:国家自然科学基金(31200853),重庆市自然科学基金(cstc2012jjA10036),重庆市卫生和计划生育委员会医学科研计划项目(2015HBRC007),国家临床重点专科建设项目[国卫办医函(2013)544].
Mechanisms of propofol-caused cognitive impairment in young obese rats
LIU Hui1,2,SUN Mang3,TIAN Qin1,ZHANG Jing1,2,CHEN Hang1,TU Sheng-fen1*
(1. Department of Anesthesiology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China;
2. Nucleic Acid and Protein Laboratory, Institute of Pediatric Research, Children's Hospital of Chongqing Medical University, Chongqing 400014, China;
3. Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Institute of Pediatric Research, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
*Corresponding author)
Abstract:
Objective To investigate the effect of propofol on cognitive function in young obese rats, and to explore its relationship with heme oxygenase 1 (HO-1), superoxide dismutase 1 (SOD1) protein expression and plasma S100 calcium-binding protein β (S100β) expression. Methods A total of 140 male SD rats aged 21 days were randomly divided into normal diet group (n=40) and high-fat diet group (n=100), and the rats were fed with a normal diet and a high-fat diet, respectively. After 4 weeks of feeding, 40 rats of the high-fat diet group with body mass ≥ the average body mass+1.4 times of the standard deviation of the normal diet group were designated as obese rats. The rats in the normal diet group were randomly divided into the normal lipid emulsion solvent group (NL group) and the normal propofol group (NP group), and the 40 obese rats were randomly divided into the obese lipid emulsion solvent group (OL group) and the obese propofol group (OP group), with 20 rats in each group. The rats in the propofol groups were intraperitoneally given propofol 100 mg/kg, and those in the lipid emulsion solvent groups (control groups) were intraperitoneally given lipid emulsion solvent 100 mg/kg, once a day for 7 days. On the first day after drug withdrawal, Morris water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group. Meanwhile, the plasma S100β protein content of each group was detected by enzyme-linked immunosorbent assay, the expression levels of HO-1 and SOD1 protein in hippocampus were detected by Western blotting, and the changes of neurons in hippocampus CA1 area were observed by hematoxylin-eosin staining. Results Compared with the OL group, the escape latency time was significantly prolonged on 1-5 days (all P<0.05), the third quadrant residence time was significantly shortened (P<0.05), the times of crossing platform was significantly decreased (P<0.05), the expression of plasma S100β protein was significantly increased (P<0.05), the relative expression levels of HO-1 and SOD1 protein in hippocampus were significantly decreased (both P<0.05), and the number of neurons in hippocampal CA1 area was significantly decreased (P<0.01) in the OP group. Compared with the NL group, the escape latency time of the NP group was significantly prolonged on 1-2 days (both P<0.05), and there were no significant differences in other indexes mentioned above (all P>0.05). Conclusion Propofol can down-regulate the expression of anti-oxidant factors HO-1 and SOD1 in the hippocampus of young obese rats, leading to increase of S100β expression and oxidative stress and eventually causing cognitive impairment.
Key words:  propofol|obesity|antioxidant factors|S100 calcium-binding protein β|cognition disorders