Abstract: Objective To investigate the effects of P165(the analog of APP5 peptide) and rosiglitazone on the expression of insulin signaling pathway related factors IRS-1 and p-CREB in SH-SY5Y cells after streptozotocin(STZ)-induced injury. Methods Human neuroblastoma cell line SH-SY5Y cells were divided into four groups: control group, STZ injury group(STZ 0.8 mmol/L), rosiglitazone protection group(STZ 0.8 mmol/L+rosiglitazone 20 μmol/L) and P165 protection group(STZ 0.8 mmol/L+P165 30 μmol/L), and were observed for morphology of cells and the immunofluorescence staining of IRS-1 and p-CREB, and we determined mean optical density using Image-pro plus software. Results Compared with the control group, cells of STZ injury group grew and divided slower, cell processes were shorter and the cell body shrunk, the intensity of immunofluorescence staining of IRS-1 and p-CREB were reduced. Compared with STZ injury group, the cells in two protection groups had neurite extension and ameliorated in cell body shrinkage and morphology, and showed stronger immunofluorescence staining. The mean optical density of IRS-1 and p-CREB in STZ injury group decreased than that of the control group(P<0.008), and the density in two protection groups increased compared with STZ injury group (P<0.008). Conclusion P165 and rosiglitazone could ameliorate the STZ-induced injury to SH-SY5Y by improving the expression of IRS-1 and p-CREB, and thereby protect the neurons.

Key words: P165, rosiglitazone, streptozotocin, insulin receptor substrate-1, phosphated-cAMP response element binding protein