丙泊酚对未成年肥胖大鼠认知功能及海马Aβ、Tau蛋白的影响  

Effects of propofol on cognitive function and hippocampal Aβ,Tau protein in young obese rats

作　　者：田芹 杨飞[1] 孙茫[2,3] 刘辉 李上莹莹 陈杭 于晴[2,3] 涂生芬[1,4,5] TIAN Qin;YANG Fei;SUN Mang;LIU Hui;LI Shang-ying-ying;CHEN Hang;YU Qing;TU Sheng-fen(Department of Anesthesiology,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China;Children’s Hospital of Chongqing Medical University,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China;Ministry of Education Key Laboratory of Developmental 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医院麻醉科,重庆400014 [2]重庆医科大学附属儿童医院儿童发育重大疾病国家国际重大科技合作基地,重庆400014 [3]重庆医科大学附属儿童医院儿童发育疾病研究教育部重点实验室,重庆400014 [4]重庆医科大学附属儿童医院国家儿童健康与疾病临床医学研究中心,重庆400014 [5]重庆医科大学附属儿童医院儿科学重庆市重点实验室,重庆400014

出　　处：《中国临床药理学杂志》2020年第14期2085-2088,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(31200853);国家临床重点专科建设基金资助项目([2013]544);重庆市自然科学基金资助项目(cstc2012jjA10036);重庆市卫计委高端人才后备基金资助项目(2015HBRC007)。

摘　　要：目的探讨丙泊酚对未成年肥胖大鼠认知功能的影响,并分析其与海马β淀粉肽样蛋白、Tau蛋白表达水平的相关性。方法大鼠普通饲料喂养作为普通组(实验组1,2),用高脂饲料喂养建立肥胖大鼠模型(实验组3,4)。按照体重建模成功后,将大鼠分为4组:实验组1、实验组2、实验组3和实验组4,每组20只;实验组1和实验组3腹腔注射等量10 mL·kg^-1脂肪乳,实验组2和实验组4腹腔注射100 mg·kg^-1丙泊酚,qd,连续给药1周。用水迷宫实验检测大鼠的认知功能,用TUNEL染色检测海马区神经元细胞凋亡情况,用蛋白质印迹法分别检测海马区β淀粉肽样蛋白(Aβ)、磷酸化Tau蛋白(p-Tau)及Tau蛋白的表达水平。结果给药后,实验组1、实验组2、实验组3和实验组4的穿越平台次数分别为(2.25±0.25),(2.00±0.21),(2.08±0.26)和(0.67±0.14)次;目标象限停留时间分别为(26.08±1.59),(26.33±1.17),(28.17±1.53)和(15.83±1.32)s;β淀粉肽样蛋白相对表达量分别为0.46±0.03,0.52±0.03,0.57±0.02,1.18±1.10;总Tau蛋白相对表达量分别为0.25±0.11,0.30±0.09,0.45±0.09,1.41±0.17;p-Tau相对表达量分别为0.35±0.05,0.38±0.03,0.48±0.03,1.60±0.11。上述指标,实验组4与实验组2比较或者实验组3与实验组4相比,差异有统计学意义(均P<0.01)。结论丙泊酚可引起未成年肥胖大鼠长期认知功能损害,其可能与增加β淀粉肽样蛋白和Tau蛋白表达有关。Objective To explore the effect of propofol on cognitive function in young obese rats,and to analyse its relationship to the expression ofβ-amyloid peptide protein,phosphorylated Tau protein and Tau protein in hippocampal tissue.Methods The rats fed with normal-diet were included in the normal group(Test 1 group,Test 2 group).Obese rats model was established by feeding the other SD rats with high-fat-diet(Test 3 group,Test 4 group).After the model was successfully eatablished,rats were randomly divided into 4 groups:Test 1 group,Test 2 group,Test 3 group and Test 4 group,each group had 20 rats.Test 1 group and Test 3 group were given intraperitoneal injection of 10 mL·kg^-1 lipid emulsion.Test 2 group and Test 4 group were given intraperitoneal injection of 100 mg·kg^-1 propofol.All groups were treated once daily for one week.Cognitive function was detected by water maze test;the neuronal apoptosis in hippocampus were detected by TUNEL method;the expression ofβ-amyloid peptide protein(Aβ),phosphorylated Tau(p-Tau)and Tau protein in hippocampal tissue were detected by Western blot.Results After administration,the times of crossing the platform in Test 1 group,Test 2 group,Test 3 group and Test 4 group were(2.25±0.25),(2.00±0.21),(2.08±0.26),(0.67±0.14)times,respectively;the retention time of target quadrant in the above four groups were(26.08±1.59),(26.33±1.17),(28.17±1.53),(15.83±1.32)s,respectively;the expression of Aβprotein in the above four groups were 0.46±0.03,0.52±0.03,0.57±0.02,1.18±1.10,respectively;the expression of phosphorylated Tau protein in the above four groups were 0.35±0.05,0.38±0.03,0.48±0.03,1.60±0.11;the expression of total Tau protein in the above four groups were 0.25±0.11,0.30±0.09,0.45±0.09,1.41±0.17.There were significant differences between Test 4 group and Test 2 group or Test 3 group and Test 4 group in the above indices(all P<0.01).Conclusion Propofol can induce long-term impairment of cognitive function in young obese rats,and it may be related to increase

关 键 词：丙泊酚 肥胖 认知功能 β淀粉肽样蛋白 TAU蛋白 

分 类 号：R97[医药卫生—药品]