Abstract: Objective: To construct the apoptosis model of islet INS-1 cells of the rats induced by dexamethasone(Dex),and to investigate the effect of lithium chloride(LiCl) on the apoptosis of the islet β cells induced by Dex and its possible mechanism. Methods: The INS-1 cells were divided into control group,0.1 μmol·L^-1 Dex group and LiCl+0.1 μmol·L^-1 Dex group. TUNEL staining and Annexin Ⅴ/PI staining methods were used to detect the apoptotic rates of the INS-1 cells in various groups;Real-time PCR method was used to detect the expression levels of superoxide dismutase (SOD),inducible-nitric oxidesynthase (iNOS),NADPH oxidase 4 (Nox4),NADPH oxidase (p47phox),and glycogen-synthase kinase-3β (GSK3β) mRNA in the INS-1 cells in various groups;Western blotting method was used to detect the expression levels of GSK-3β,p-GSK-3β,SOD,iNOS and Nox4 proteins in the INS-1 cells in various groups;GENMED Kit was used to detect the levels of reactive oxygen species (ROS) in the INS-1 cells in various groups,and Griess method was used to detect the levels of nitric oxide (NO) in the INS-1 cells in various groups. Results: Compared with control group,the apoptotic rate of INS-1 cells in 0.1 μmol·L^-1 Dex group was significantly increased(P<0.05),the expression levels of SOD mRNA and p-GSK-3β proteins were decreased(P<0.05),the expression levels of Nox4,p47phox,iNOS mRNA were increased(P<0.05),and the expression levels of ROS and NO in the INS-1 cells were significantly increased (P<0.05); compared with 0.1 μmol·L^-1 Dex group,the apoptotic rate of INS-1 cells in LiCl+0.1 μmol·L^-1 Dex group was significantly decreased(P<0.05),the expression levels of SOD mRNA and p-GSK-3β protein were increased(P<0.05),the expression levels of Nox4,p47phox and iNOS mRNA were decreased(P<0.05 or P<0.01),and the levels of ROS and NO were decreased (P<0.05). Conclusion: Dex can induce the apoptosis of the islet β cells of the rats.LiCl can attenuate the apoptosis of dexamethasone-induced islet β cells by inhibiting the activity of GSK-3β.

Key words: lithium chloride, glycogen synthase kinase-3β, dexamethasone, apoptosis, INS-1 cells