Adiponectin improves isoflurane-induced cognitive dysfunction in elderly rats via inhibiting p38-MAPK signal pathway in hippocampus

J.-C. Zhang, W.-J. Zhang, Q. Zhao, B.-N. Chen, X. Wang, Y.-P. Luo, F.-X. Zhang

Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, China. zfx1205@126.com

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• Geriatrics

OBJECTIVE:  To investigate the intervention of exogenous adiponectin in the elderly rats with cognitive dysfunction induced by isoflurane through mitogen-activated protein kinase (MAPK) signaling pathway in hippocampus.

MATERIALS AND METHODS: A total of 60 healthy elder Sprague Dawley (SD) rats aged 15-20 months and weighing 400-500 g were selected. These rats were randomly divided into four groups, i.e., the control group, the anesthetic group, adiponectin intervention group, and p38-MAPK antagonist group, in which the rats in the control group were treated through inhalation of pure oxygen for 4 h at a rate of 4 L/min, while the rats in the other 3 groups were treated through inhalation of isoflurane for 4 h. During the inhalation of isoflurane, the concentration of isoflurane was 3.5% at the beginning and decreased to 2.2% at 1 h, and 1.7% between 2 h and 4 h. Then, the intraperitoneal injection of 0.5 mL normal saline was performed for the rats in the control group and the anesthetic group, while adiponectin (300 mg/kg) was injected into the rats in the adiponectin intervention group and p38-MAPK antagonist group. Simultaneously, the antagonist (20 mg/kg) diluted to 0.5 mL was given to the rats in the p38-MAPK antagonist group, once/day for 3 days. Morris water maze test was carried out respectively in the 1st, 3rd, and 7th day, and 5 rats participated in the test at each time point, during which we recorded the escape latency, as well as the length of the swimming route of rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the mRNA and protein expressions of p38 in the hippocampus.

RESULTS: The escape latency and the length of the swimming route at any time point after the intervention in the anesthetic group were significantly longer than those in the control group (p<0.05), and they were significantly shorter in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05). The mRNA and protein expressions of p38 at any time point after intervention in the anesthetic group were higher than those in the control group (p<0.05), and they were significantly lower in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05).

CONCLUSIONS: Exogenous adiponectin can improve the cognitive dysfunction of the elderly rats after anesthesia using isoflurane, possibly by inhibiting the p38-MAPK signal pathway in hippocampus.

Published on: 2019/08/07

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