EFFECT OF SILENCE INFORMATION REGULATOR 3 (SIRT3) ON OXIDATIVE STRESS AND APOPTOSIS OF RENAL TUBULAR EPITHELIAL CELLS IN HIGH GLUCOSE ENVIRONMENT AND ITS POSSIBLE MECHANISM INVESTIGATION

Hualing Ruan¹, Kunquan Guo¹, Zhengdong Li², Huaqian Chen², Kun Yang¹, Linxiu Ye¹, Lirong Zhou¹, Li Zhao^{2, *}

¹Department of Endocrinology, Affliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, PR China - ²Department of Nephrology, Affliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, PR China

Objective: The objective is to analyse the effects and possible mechanisms of silent information regulator 3 (SIRT3) on oxidative stress and apoptosis in renal tubular epithelial cells in a high glucose environment.

Methods: The diabetic rat model was established, and both the diabetes and control groups were randomly divided into 8-week and 12-week groups. The expression of SIRT3 mRNA and protein in the kidneys of the rats in each group was detected using the real-time quantitative PCR and western blot assay techniques. Renal tubular epithelial cells were cultured in vitro for plasmid transfection and were divided into a control group, SIRT3 transfection group, HG control group, and HG SIRT3 transfection group. The expression of superoxide dismutase 2 (SOD2), catalase, Bcl-2, Bax, Fas-L, Akt, FoxO1, and FoxO3a proteins in renal tubular epithelial cells was detected using a western blot assay.

Results: The levels of SIRT3 mRNA and protein in the kidneys of the 8-week diabetes group were significantly higher than those of the 8-week control group (P<.05). The level of SIRT3 mRNA and protein in the 12-week diabetes group was remarkably lower than that in the 12-week control group (P<.05). The expression levels of SOD2 and catalase protein in the HG SIRT3 transfection group were obviously higher than those in the HG control group (P<.05). The expression levels of SBcl-2, Bax, and Fas-L proteins in the HG SIRT3 transfection group were significantly lower than those in HG control group (P<.05). The expression levels of Akt, FoxO1, and FoxO3a proteins in the HG SIRT3 transfection group were markedly higher than those in HG control group, and the differences were statistically significant (P<.05).

Conclusion: In summary, SIRT3 is involved in the process of diabetic nephropathic injury, and its overexpression can significantly reduce the oxidative stress and apoptosis of renal tubular epithelial cells in a high glucose environment. Its related mechanism may be related to the regulation of the Akt/FoxO signalling pathway, thus acting as an antioxidant with an anti-apoptotic effect.