Objective: To investigate the effects of metformin(Met) on neuron autophagy and cognitive function in infant rats anesthetized with sevoflurane(Sev). Methods: MTT method was used to detect the effective dose of Met to improve the viability of SH-SY5Y cells induced by Sev, and to determine the effect of Met on the expression of autophagy/apoptosis-related proteins in SH-SY5Y cells. Then sixty SD infant rats were randomly divided into control(Con) group, Sev group, Met group, Met+rapamycin(Met+Rap) group, Met+chloroquine(Met+CQ) group. The infant rats in each group were anesthetized with 3% Sev, then, blood gas analysis was performed. The infant rats received drug treatment for continuous 7 days, during which the water maze was used to detect the cognition impairment, the Nissl staining was used for neuron status detection. Western blotting and immunofluorescence were used to detected autophagy/apoptosis-related protein expression. Results: Met effectly improved SH-SY5Y cells viability that induced by Sev and Met effectively inhibited the expression of Caspase-3, Bax(P<0.05), as well as down-regulated mTOR, LC3-Ⅱ/LC3-Ⅰ expression(P<0.05). During anesthesia, the blood gas indexes of rats were similar(P>0.05).Compared with Sev group,the expressions of Caspase-3, Bax, mTOR, LC3-Ⅱ/LC3-Ⅰ in Met group were lower and escape latency was shorter(P<0.05). Meanwhile, Rap played a synergistic role with Met. However, the administration of CQ exerted an antagonistic effect on Met. Conclusion: Met effectively improve cognitive dysfunction in infant rats caused by Sev through activating neuron autophagy pathway. |
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