丙泊酚对老年痴呆大鼠AMPK自噬通路及认知功能的影响

doi:10.3969/j.issn.1006-6233.2021.01.006

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (1624 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: 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 words： Propofol Alzheimer's disease AMPK Autophagy Cognitive function

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2021.01.006 OR http://www.hbyxzzs.cn/EN/Y2021/V27/I1/23

[1] Neth BJ, Mintz A, Whitlow C, et al. Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study[J]. Neurobiol Aging, 2020, 86(1):54~63.
[2] Kfoury A, Armaro M, Collodet C, et al. AMPK promotes survival of ccmyc ositive melanoma cells by suppressing oxidative stress[J]. Embo, 2018, 37(5):e97673.
[3] Foretz M, Viollet B. Activation of AMPK for a break in hepatic lipid accumulation and circulating cholesterol[J]. Ebiomedicine, 2018, 31(1):15~16.
[4] Majd S, Power JHT. Oxidative stress and decreased mitochondrial superoxide dismutase 2 and peroxiredoxins 1 and 4 based mechanism of concurrent activation of AMPK and mTOR in alzheimer's disease[J]. Curr Alzheimer Res, 2018, 15(8):764~776.
[5] Zhang X, Xie Y, Xu W, et al. Effects of 5-Aza on p-Y1472 NR2B related to learning and memory in the mouse hippocampus[J]. Biomed Pharmacother, 2019,109(1):701~707.
[6] 张昕,林春水,郭培培,等.丙泊酚对SD乳鼠少突胶质细胞髓鞘碱性蛋白表达和髓鞘形成的影响[J].南方医科大学学报,2019,39(8):950~956.
[7] 李虹霖,高伟,夏昆鹏,等.头穴丛刺对阿尔茨海默病大鼠海马区ChAT、AchE表达的影响[J].中国针灸,2019,39(4):403~408.
[8] 谭宇亭,刘兰,廖芸茜,等.白藜芦醇对新生大鼠七氟烷麻醉后认知功能改变的影响[J].解放军医学杂志,2018,43(7):600~606.
[9] 马佳呈,李炜,张丹参.老年痴呆症的发病机制研究[J].中国药理学与毒理学杂志,2019,33(6):469~470.
[10] Kuang H, Tan CY, Tian HZ, et al. Exploring the bi-directional relationship between autophagy and Alzheimer's disease[J]. Cns Neurosci Ther, 2020, 26(1):155~166.
[11] Lin L, Huang S, Zhu Z, et al. P2X7 receptor regulates EMMPRIN and MMP-9 expression through AMPK/MAPK signaling in PMA-induced macrophages[J]. Mol Med Rep, 2018, 18(3):3027~3033.
[12] Jun SD, Hee NY, Ho LJ, et al. Diet control to achieve euglycaemia induces tau hyperphosphorylation via AMPK activation in the hippocampus of diabetic rats[J]. Food Funct, 2020, 11(1):339~346.
[13] Jang CH, Lee S, Park Y, et al. Memantine attenuates salicylate-induced tinnitus possibly by reducing NR2B expression in auditory cortex of rat[J]. Exp Neurobiol, 2019, 28(4):495~503.