The Role Of SIK1 In Type 2 Diabetic Nephropathy With Hypertension

Objective:To observe the expression of SIK1,Na~+,K~+-ATPaseα1 and Na~+,K~+-ATPase activity in the kidney tissue of diabetic nephropathy with hypertension rats model and the influence of staurosporine and gliquidone on expression of SIK1 .Methods:The model rats of type 2 diabetic were established by feeding high fat diet and injecting 45 mg/kg streptozotocin. The successful model rats were randomly divided into model group,Staurosporine group and gliquidone group(9 or 10 each). Another 10 normal rats were as normal control group.Consecutive administration for 12 weeks.Observed the item of fastingblood glucose(FBG),postprandial glucose(PBG),serum triglyceride (TG), total cholesterol (TC), and insulin (FINS), insulin sensitivity index(ISI),24h urine albumin,serum creatinine and urinary creatinine, endogenous creatinine clearance rate(Ccr)and tail arterial blood pressure . At the end of the experiment, rats were sacrificed, calculating kidney weight index and observing tissues pathology;the expression of SIK1 protein was determined by immunohistochemistry and expression of SIK1,Na~+,K~+-ATPaseα1mRNA was determined by RT -PCR;Na~+,K~+-ATPase activity was detected simultaneously .Results:1.After 4 weeks high fat diet, compared with normal control group, model group FBG was no significant difference(P>0.05), TG,TC and FINS increased significantly (P <0.05, P < 0.01), ISI decreased significantly (P < 0.05);One week after STZ injection,model group FBG was significantly higher (P <0.01). 2.After treating for 6,12 weeks , compared with normal control group, model group FBG, PBG, TG, TC increased significantly(P <0.01); compared with model group, Staurosporine group FBG, PBG, TC decreased significantly ( P <0.01 or P<0.05),TC was no significant difference (P> 0.05); gliquidone group FBG, TG, TC decreased significantly (P <0.01 or P <0.05), but PBG was no significant difference (P> 0.05).3.After treating for 6,12 weeks,compared with the normal control group, model group blood pressure was increased significantly(P<0.05); Compared with the model group, Staurosporine group and gliquidone group blood pressure reduced significantly (P <0.05).4.Compared with the normal control group, model group Ccr was significantly reduced (P <0.01); UAE, KI was significantly increased (P <0.01); Compared with model group, Staurosporine group and gliquidone group Ccr was significantly higher (P <0.01), UAE, KI were significantly lower (P <0.05).5.Pathology results showed that normal group glomerular and tubular structure was normal; the model group showed a different degrees of glomerular increased , glomerular capsuls and mesangial region widened, glomerular basement membrane thickened ; renal tubular epithelial cell swelling, interstitialinflammatory cells infiltrated ; Staurosporine group and gliquidone group, these pathological changes have varying degrees of reducing,glomerular and tubular swelling was lighted and thicked basement membrane was improved .6.Compared with the normal control group, expression of SIK1 mRNA and protein in model grouprenal tissue were increased significantly(P <0.01), Na~+,K~+-ATPaseα1 mRNA and Na~+,K~+-ATPase activity were increased significantly(P <0.01);Compared with model group, Staurosporine group SIK1 mRNA and protein,Na~+,K~+-ATPase activity were no significant difference (P> 0.05), but in gliquidone group, these indexes decreased and the difference was statistically significant (P <0.01 or P<0.05).Conclusion:The expression of SIK1 mRNA and protein in renal tissue of type 2diabetic nephropathy with hypertension rats model was increased ,may itself or by regulating Na~+,K~+-ATPase activity which involved in the development of diabetic nephropathy and hypertension ; Staurosporine had no effects on the expression of SIK1 ,gliquidone group SIK1 mRNA and protein, Na~+,K~+-ATPaseα1 mRNA and Na~+,K~+-ATPase activity were decreased.This two group can reduced some the biochemical index and improved renal function items and renal pathology.