Hydrogen Sulfide Promotes Hippocampal Neurogenesis In Diabetic Rats Though The PI3K/Akt Pathway

[Objective]To explored whether the PI3K/Akt pathway inhibitor LY294002 can reverse the improvement of H₂S in hippocampal neurogenesis in diabetic rats,and further verified whether the PI3K/Akt signaling pathway mediates H₂S to improve hippocampal neurogenesis in diabetic rats.[Methods]1.STZ was intraperitoneally injected into the rats to model diabetic rats.2.SD rats were divided into five groups:control group,STZ group,STZ+NaHS（100μmol/kg/d,i.p.）group,STZ+NaHS+LY294002（2 ug/2d,i.c.v.）group,LY294002（2 ug/2d,i.c.v.）group.3.The expressions of PI3K/Akt pathway-associated proteins total AKT,p-ser473-Akt and hippocampal neurogenesis-associated proteins DCX,NeuN,GFAP were tested by WB.[Results]1.LY294002 did not affect the expression of PI3K/Akt pathway-related protein total AKT in STZ-induced diabetic ratsThere was no significant difference in the expression level of PI3K/Akt pathway related protein total AKT in diabetic rats compared with the control group（P>0.05）.After treated with NaHS,there was no significant difference in the expression level of PI3K/Akt pathway related protein total AKT in diabetic rats（P>0.05）.LY294002 also did not affect the expression of total AKT related proteins in the PI3K/Akt pathway in diabetic rats（P>0.05）.2.LY294002 reversed H₂S-upregulated hippocampal PI3K/Akt pathway-associated proteins p-AKT expression in STZ-induced diabetic ratsThe expression level of PI3K/Akt pathway related protein p-AKT in diabetic rats was significantly reduced compared with the control group（P<0.05）.After treated with NaHS,the expression level of PI3K/Akt pathway related protein p-AKT in diabetic rats was increased（P<0.05）.However,LY294002 reduced the expression of NaHS on p-AKT related protein of PI3K/Akt pathway in diabetic rats（P<0.05）.3.LY294002 reversed H₂S-upregulated hippocampal neurogenesis-associated proteins DCX expression in STZ-induced diabetic ratsThe expression of hippocampal neurogenesis-related protein DCX in diabetic rats was significantly reduced compared with the control group（P<0.05）.After treated with NaHS,the expression of hippocampal neurogenesis-related protein DCX in diabetic rats was increased（P<0.05）.However,LY294002 reduced the expression of NaHS in the hippocampal neurogene-related protein DCX in diabetic rats（P<0.05）.4.LY294002 reversed H₂S-upregulated hippocampal neurogenesis-associated proteins NeuN expression in STZ-induced diabetic ratsThe expression of hippocampal neurogenesis-related protein NeuN in diabetic rats was significantly reduced compared with the control group（P<0.01）.After treated with NaHS,the expression of hippocampal neurogenesis-related protein NeuN in diabetic rats was increased（P<0.01）.However,LY294002 reduced the expression of NaHS in the hippocampal neurogene-related protein NeuN in diabetic rats（P<0.05）.5.LY294002 reversed H₂S-downregulated hippocampal neurogenesis-associated proteins GFAP expression in STZ-induced diabetic ratsThe expression of hippocampal neurogene-related protein GFAP in diabetic rats was significantly increased compared with the control group（P<0.05）.After treated with NaHS,the expression of hippocampal neurogene-related protein GFAP in diabetic rats was decreased（P<0.01）.However,LY294002 significantly increased the expression of NaHS on hippocampal neurogene-related protein GFAP in diabetic rats（P<0.01）.[Conclusion]Hydrogen sulfide promotes hippocampal neurogenesis in diabetic rats through the PI3K/Akt pathway.