The Expression Of Serum And Glucocorticoid-inducible Kinase1 In Diabetic Rats And Its Modulation By Fluvastatin

PartⅠExpression of SGK1 and CTGF and their correlation in renal cortex of diabetic rats【Objective】To examine the expression of serum and glucocorticoid-inducible protein kinase 1(SGK1) in the renal cortex of diabetic rats, and to investigate the signal pathway mediated by SGK1 in diabetic nephropathy.【Methods】64 male Wistar rats were randomly divided into control group and diabetic group, The diabetic rats were given a bolus intraperitoneal injection of 65 mg/kg of streptozotocin dissolved in citrate buffer(pH=4.8). 48 hours later, hyperglycermic rats with glucose levels≥16.7mmol/L were selected into diabetic group. At 0 week, 2 weeks, 4 weeks and 8 weeks, the metabolic data were measured, and immunohistochemistry was used to examine the expression of transforming growth factorβ1(TGF-β1) and fibronectin (FN). The expression of SGK1 was detected by RT-PCR and Western blot, and CTGFmRNA was assessed by RT-PCR .【Results】Clearance rate of creatinine(Ccr) increased at 4 weeks while 24 hours urinary protein significantly increased at 8 weeks(P<0.01), the expression of TGF-β1, FN, CTGF and SGK1 increased more and more at 0 week, 2 weeks, 4 weeks and 8 weeks(P<0.01). The expression of SGK has positive correlation with CTGF, TGF-β1 and FN(P<0.01).【Conclusion】SGK1 expression is markedly upregulated in the renal cortex of diabetic rats, and may play an important role in the development and process of diabetic nephropathy. PartⅡThe observation of the decrease of SGK1 expression by fluvastatin in the renal cortex of diabetic rats【Objective】To observe the modulation of Serum and glucocorticoid-inducible kinase1 (SGK1) by fluvastatin, and to investigate the protective effect of fluvastatin on the signal pathway mediated by SGK1.【Methods】24 male Wistar rats were randomly divided into normal control group(n=8), diabetic nephropathy group(n=8) and fluvastatin-treated diabetic neph- ropathy group(15mg·kg-1·d-1, n=8). The metabolic data were measured at week 8. Immunohistochemistry was used to examine the expression of transforming growth factorβ1(TGF-β1) and fibronectin (FN). The expression of SGK1 was detected by RT-PCR and Western blot, and CTGFmRNA was assessed by RT-PCR .【Results】As compared to DN, 24h urinary protein, Ccr and kidney weight index were all decreased and the weight was increased obviously in F group(P<0.01). At the same time, mesangial cell and extracellular matrix proliferation were relieved significantly(P<0.01). The levels of cortex SGK1 mRNA and protein were up-regulated, TGF-β1 and FN were down-regulated by fluvastatin(P<0.01).【Conclusion】Fluvastatin suppressed the increased SGK1 mRNA and protein expressions in renal cortex, and perhaps postponed the development of diabetic nephropathy by suppressing intra-cellular signal transduction.