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.
ABSTRACT
Aim To investigate the effect of berberine on the expression of nephrin, podocin and intergrinα3β1 in diabetic nephropathy ( DN ) rat model, and further probe in to the renoprotective effects of berber-ine and its potential mechanisms. Methods The rat model of DN was induced by intraperitoneal injection of streptozotocin ( STZ ) after fed with high-sugar and high-fat diet for six weeks. The rats were assigned into 6 groups randomly: normal control group, DN model group, BBR (50,100 and 200 mg·kg-1 ) treatment group and enalaprilat positive control group ( 1 mg · kg-1 ) . The distribution and expression of kidney podocyte related proteins nephrin, podocin and interg-rinα3β1 were detected by immunohistochemical meth-od following electron microscopy observation ( × 1000 ) and high magnification observation( × 400) and West-ern blot. Results The podocyte related protein neph-rin, podocin and intergrin α3β1 were mainly distribu-ted in podocyte, but slightly different. Compared with normal control group, the expresion of podocyte related protein nephrin, podocin and intergrin α3β1 was de-creased obviously; compared with model group, BBR (100 and 200 mg·kg-1 ) treatment group could sig-nificantly suppress the abnormalities of pathological changes of the kidney and upregulate the expression levels of podocyte specific protein nephrin, podocin and intergrin α3β1 in the kidney of diabetic rats with nephropathy. Conclusions Berberine could alleviate the abnormalities of kidney pathological changes and proteinuria production in the DN model rats, which may be related to the upregulation of the expression of the podocyte proteins nephrin, podocin and intergrinα3β1.