Expression Of SIK1in The Kidney Of Diabetic Rats And Intervention Effects Of Metformin And Zhenqing Recipe

Objective: To observe the expression of renal salt-inducible kinase (SIK1) and sterolregulatory element binding protein (SREBP-1c) in diabetic rats. Studying theregulation of Metformin and Zhenqing Recipe on renal lipid metabolism andinvestigating its possible molecular mechanism.Methods: The male Wistar rats were induced by high-sucrose-high-fat feeding andintraperitoneal injection of low dose STZ to establish type2diabetic rats, randomlydivided into normal control group, model group, Zhenqing Recipe treatment groupand metformin treatment group. After high energy diet for one month and STZinjection after three days, detecting fasting blood glucose (FBG)、blood lipids(TC,TG) level、blood insulin (FINs) level and insulin sensitivity index (ISI) of each grouprats were measured; After12weeks of administration, investigating the changes ofFBG、TG、TC、serum creatinine (Scr)、urinary creatinine (Ucr), and then theendogenous creatinine clearance rate (Ccr) was calculated. Weighing the rats beforesacrificed, and then calculating the kidney weight index (KI); Determinating TGcontent in the renal cortex, Using HE staining and immunohistochemical to observethe structural changes of renal tissue and the location of SIK1expressed; RT-PCR andWestern blotting were used to determine mRNA and protein expression of SIK1andSREBP-1c in renal cortex. Results:1、After high energy for1month, FBG in model group rats was no significantdifference compared with normal group (P>0.05), the serum TG、TC and FINS wereincreased significantly(P <0.05or P <0.01), ISI was reduced significantly(P<0.01);Injection STZ for3days, FBG in model group was significant higher compared withnormal group(P<0.01), FINS was no significant diffirence in model group, but stillhigher than normal group.(P>0.05).2、After model12weeks, compared with normal group, the FBG, TG, TC, UAE, KIand renal cortex of TG levels were significantly increased in model group (P <0.05orP <0.01), the Ccr was significantly decreased (P <0.05); Compared with model group,the FBG, TG and TC were significantly decreased (P <0.05or P <0.01), renal cortexof TG were significantly reduced (P <0.01) both in Zhenqing Recipe group andmetformin group; The UAE and KI in Zhenqing Recipe and metformin group weresignificantly lower than that of model group (P <0.01, P <0.05), while Ccr wassignificantly higher (P <0.05).3、The morphology of the renal tissue showed that glomerular volume was increased,mesangial matrix was proliferated and capillary basement membrane was thicken;these pathological changes was significant changed in Zhenqing Recipe group andmetformin group.4、The results of immunohistochemistry showed that SIK1was expressed mainly inrenal tubular of diabetic rats, and a small amount of expression in glomerular. Theexpression of SIK1mRNA and protein in model group was significantly decreasedcompared with normal group, and the SREBP-1c expression was significantlyincreased. Compared with model group, the expression of SIK1mRNA and proteinwas significantly elevated both in Zhenqing Recipe and metformin group, and asignificant reduction of SREBP-1c expression.Conclusion: SIK1is mainly expressed in renal tubular of diabetic rat, and lessexpressed in renal glomerular. Metformin and Zhenqing Recipe can significantlyreduce serum glucose, serum lipids and UAE, inhibit diabetic nephropathy; Thepossible mechanism is that raised the expreesion of SIK1, inhibited SREBP-1c and then reduced lipid deposition in the renal tissue.