Effects Of Intraperitoneal Injection Of Resveratrol On Lysosome Function In Cerebral Cortex

Aim: To study the effect of resveratrol on lysosome function and biosynthesis of mouse cerebral cortex and to explore the molecular mechanism.Methods: Intraperitoneal injection of resveratrol was performed once every day for 3 days as a short-term administration model,and 30 days as a long-term administration model.First,evaluate the effect of short-term administration model on the autophagic lysosome pathway of mouse cerebral cortex,and detect the changes of autolysosome-associated protein level by western blot,including the autophagosome-forming marker protein LC3,autophagy substrate P62 and the lysosomal membrane protein LAMP1.Subsequently,the effects of long-term administration models on the lysosomal function and biosynthesis of mouse cerebral cortex were evaluated.The levels of LAMP1,cathepsin Cathepsin D and Cathepsin L and transcription factor TFEB were measured by western blot,and q PCR was used to detect the gene transcription levels regulated by TFEB.Finally,the molecular mechanism of resveratrol affecting lysosome function was analyzed.The effect of resveratrol and SIRT1 inhibitor Ex527 on the activity of SIRT1 was analyzed.The relationship between SIRT1 and TFEB was explored,and the analysis of resveratrol and Ex527 against TFEB was performed.Nuclear and lysosome-related gene transcription effects.Results: Western blotting results showed that short-term intraperitoneal injection of resveratrol could significantly activate the expression of autophagosome marker LC3 II and lysosomal marker LAMP1,and significantly inhibited the expression of autophagic substrate P62;long-term intraperitoneal injection of resveratrol not only can significantly up-regulate the expression of LAMP1,the expression level of activated lysosomal cathepsin Cathepsin D and Cathepsin L also increased significantly,in addition,long-term intraperitoneal injection of resveratrol can also promote the entry of TFEB into the nucleus and increase the transcription of genes level regulated by TFEB.Resveratrol can significantly activate SIRT1 activity and promote TFEB entry into the nucleus;SIRT1 inhibitor Ex527 has no effect on TFEB nuclear entry,but it can inhibit the transcription of the target gene regulated by TFEB.Conclusion: Resveratrol can enhance the function of lysosomes by promoting the nuclear import of TFEB,activating SIRT1,enhancing the transcriptional activity of TFEB,and up-regulating the autosomal lysosome-related genes.