Effects of metformin on SIRT1 expression of renal tissues in type 2 diabetic rats / 中国药理学通报

ABSTRACT

Aim To observe the effects of metformin (MET) on the silencing regulatory protein 1 (SIRT1) mRNA and protein expression in renal tissues of type 2 diabetic mellitus (T2DM) rats, and explore its reno-protective mechanisms. Methods Thirty model T2DM rats were randomly divided to glibenclamide in-tervention group (GLY group, 5 mg·kg-1·d-1), metformin intervention group (MET group,300 mg· kg-1· d-1) and diabetic control group (T2DM group),and 10 rats with normal glucose tolerance were used as normal control(NC group). After 8 weeks, HbA1c,blood glucose (BG), urea nitrogen (BUN), urinary albumin, creatinine and glomerular basement membrane thickness (GBMT) were detected. The ex-pression of SIRT1 protein in renal tissues was detected by immunohistochemistry, the expression of SIRT1 mRNA in renal tissues was detected by real-time PCR, and urinary SIRT1 protein was detected by ELISA. Results At the end of 8 weeks, the levels of BG,HbA1c,urinary albumin/urinary creatinine(UACR), urinary SIRT1/urinary creatinine (USIR) and GBMT in MET and GLY groups were significantly lower than those in T2DM group (P<0.05). There was no sig-nificant difference in BG, HbA1c and GBMT between MET group and GLY group (P>0.05). The expres-sions of SIRT1 mRNA and protein in MET group were significantly lower than those in NC group (P <0.05), but higher than those in T2DM group (P <0.05). The UACR, expression of SIRT1of renal tis-sues in MET group was higher than that in GLY group (P<0.05),but urinary SIRT1 protein was lower than that in GLY group (P <0.05). Conclusion Met-formin can increase the expressions of SIRT1 in renal tissues of T2DM rats,which may be related to its renal protection.