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河北医学  2021, Vol. 27 Issue (1): 23-27    DOI: 10.3969/j.issn.1006-6233.2021.01.006
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丙泊酚对老年痴呆大鼠AMPK自噬通路及认知功能的影响
郑仲磊, 张万平, 苏玉强, 薛沙, 范晓英
西安医学院第二附属医院手麻科, 陕西 西安 710038)
Effects of Propofol on AMPK Autophagy Pathway and Cognitive Function in Alzheimer's Rats
ZHENG Zhonglei, ZHANG Wanping, SU Yuqiang, et al
The Second Affiliated Hospital of Xi'an Medical College, Shaanxi Xi'an 710038, China
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摘要 目的: 探讨丙泊酚对老年痴呆大鼠腺苷酸活化蛋白激酶(AMPK)自噬通路及认知功能的影响。方法: 清洁级SD大鼠100只,随机分成5组:对照组、模型组、盐酸米诺环素组(50mg/kg)、丙泊酚低、高剂量组(50、100mg/kg)。模型组、盐酸米诺环素组、丙泊酚低、高剂量组海马注射β样淀粉蛋白1-42(Aβ1-42)建立老年痴呆模型,建模成功后,盐酸米诺环素组、丙泊酚低、高剂量组给予相应药物灌胃,对照组、模型组灌胃等体积的生理盐水,每天1次,试验周期为4周。试验结束后,Morris水迷宫试验测定大鼠神经认知功能,将大鼠海马神经元进行HE染色进而观察其病理结构,将大鼠海马神经元进行吖啶橙染色进而观察其自噬情况,实时荧光定量PCR(RT-PCR)法及蛋白质免疫印迹(Western-blot)法测定大鼠海马组织AMPK、N-甲基-D-天冬氨酸受体2B(NR2B)mRNA和蛋白水平。结果: 对照组海马区神经元细胞较多,排列整齐;模型组海马区见片状神经元坏死,数目减少,核固缩明显;丙泊酚低剂量组坏死神经元细胞减少;盐酸米诺环素组、丙泊酚高剂量组海马区见少量坏死神经元细胞,神经元细胞结构完整。与对照组比较,模型组逃避潜伏期时间、AMPK、NR2B mRNA和蛋白表达水平明显升高,经过原平台位置的次数、原平台象限停留的时间、神经元自噬小体水平明显降低(P<0.05)。与模型组比较,盐酸米诺环素组和丙泊酚低、高剂量组逃避潜伏期时间、AMPK、NR2B mRNA和蛋白表达水平明显降低,经过原平台位置的次数、原平台象限停留的时间、神经元自噬小体水平明显升高(P<0.05)。与盐酸米诺环素组比较,丙泊酚低剂量组逃避潜伏期时间、AMPK、NR2B mRNA和蛋白表达水平明显升高,经过原平台位置的次数、原平台象限停留的时间、神经元自噬小体水平明显降低(P<0.05)。丙泊酚高剂量组与盐酸米诺环素组逃避潜伏期时间、AMPK、NR2B mRNA和蛋白表达水平、经过原平台位置的次数、原平台象限停留的时间、神经元自噬小体水平相近(P>0.05)。结论: 丙泊酚能增加老年痴呆大鼠神经元自噬水平进而明显减轻海马神经元损伤程度,其机制与丙泊酚抑制AMPK信号通路有关。
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关键词 丙泊酚老年痴呆AMPK自噬认知功能    
AbstractObjective: To investigate the effect of propofol on adenosine monophosphate-activated protein kinase (AMPK) autophagy pathway and cognitive function in Alzheimer's rats. Methods: 100 clean grade SD rats were random divided into 5 groups: control group, model group, minocycline hydrochloride group (50 mg/kg), propofol low and high dose group (50, 100mg/kg). Model group, minocycline hydrochloride group, propofol low and high dose group were hippocampus injected into Aβ1-42 to establish Alzheimer's disease model. After the model was established successfully, the rats in the minocycline hydrochloride group, propofol low and high dose group were given corresponding drugs by gavage for 4 weeks, 1 times a day. The control group and the model group were gavaged the same volume of normal saline. At the end of the experiment, Morris water maze test was used to measure the rats nerve function, HE staining to observe the pathological structure of hippocampal neurons in rats, and acridine orange staining was used to measure the rats autophagy of hippocampal neurons, and RT-PCR and Western blot were used to measure the AMPK, N-methyl-D-aspartate receptor subunit 2B(NR2B) mRNA and protein levels in hippocampal tissue of rats. Results: In the control group, there were more neuron cells in the hippocampus and they were arranged neatly; in the model group, the number of neurons in the hippocampal area was decreased and the pyknosis was obvious; the number of necrotic neurons decreased in low dose propofol group; in minocycline hydrochloride group and propofol high dose group, a small number of necrotic neurons were found in the hippocampus, and the structure of neurons was complete. Compared with the control group, the escape latency time, AMPK, NR2B mRNA and protein expression levels in the model group were significantly increased, and the number of times of passing through the original platform position, the time of staying in the original platform quadrant, and the level of autophagy bodies were significantly decreased(P<0.05). Compared with the model group, the escape latency time, AMPK, NR2B mRNA and protein expression levels in the minocycline hydrochloride group and the propofol low and high dose group were significantly decreased, and the number of times of passing through the original platform position, the time of staying in the original platform quadrant, and the level of autophagy bodies were significantly increased (P<0.05). Compared with minocycline hydrochloride group, the escape latency time, AMPK, NR2B mRNA and protein expression level of propofol low-dose group were significantly increased, and the number of times of passing through the original platform position, the time of staying in the original platform quadrant, the level of autophagy bodies of neurons were significantly decreased (P<0.05). The escape latency time, AMPK, NR2B mRNA and protein expression, the number of times of passing through the original platform position, the time of staying in the original platform quadrant, and the level of autophagy bodies were similar between the minocycline hydrochloride group and propofol high dose group (P>0.05). Conclusion: Propofol can increase the autophagy level of neurons in Alzheimer's rats and then significantly reduce the degree of Hippocampus neuron injury. The mechanism is related to the inhibition of AMPK signaling pathway by propofol.
Key wordsPropofol    Alzheimer's disease    AMPK    Autophagy    Cognitive function
    
基金资助:陕西省社会发展科技攻关项目,(编号:2016SF-166)
通讯作者: 范晓英   
引用本文:   
郑仲磊, 张万平, 苏玉强, 薛沙, 范晓英. 丙泊酚对老年痴呆大鼠AMPK自噬通路及认知功能的影响[J]. 河北医学, 2021, 27(1): 23-27.
ZHENG Zhonglei, ZHANG Wanping, SU Yuqiang, et al. Effects of Propofol on AMPK Autophagy Pathway and Cognitive Function in Alzheimer's Rats. HeBei Med, 2021, 27(1): 23-27.
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