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.
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2021, Vol. 27 
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