Protective Effects And Mechanical Study Of TZD On Kidney In Diabetic Rats

STUDY ON THE PROTECTIVE EFFECTS OF TZDON KIDNEY OF DIABETIC RATSObjective To investigate the protective effects and the mechanisms of thiazolinedine on kidneys of diabetic rats. Methods The animal model was induced by STZ.Wistar rats were randomly divided into following groups: normal control group(NC); normal control group with TZD(NCT) ;diabetic mellitus group(DM); DM group with TZD (DMT) .NCT and DMT were treated with TZD(3mg/kg.d) by gavage. 24 hour urinary protein and kidney weight to body weight ratio were detected . Glomerular extracellular matrix (ECM) accumulation and glomerular mesangial cell proliferation and base-membrane thickness were observed too.Results 24 hour urinary protein and kidney weight to body weight ratio of DM group were significantly increased as compared with NC and NCT(P<0.05). 24 hour urinary protein and kidney weight to body weight ratio of DMT were decreased as compared with DMT(P<0.05). 24 hour urinary protein and kidney weight to body weight ratio of DMT were increased as compared with NC and NCT(P<0.05).There were no significant difference between NC and NCT (P＞0.05). Glomerular extracellular matrix (ECM) accumulation and glomerular mesangial cell proliferation and base-membrane thickness in diabetic group were significantly higher than the other groups.(P<0.05). Glomerular extracellular matrix (ECM) accumulation and base-membrane thickness and glomerular mesangial cell proliferation is decreased after treatment of TZDs. Conclusions TZD ( pioglitazone) can inhibit Glomerular extracellular matrix (ECM) accumulation and synthesis of base-membrane matrix and glomerular mesangial cell proliferation on diabetic kidney tissue .So TZD has protective effects on kidney of rats. PART TWOTHE EFFECT OF TZD ON APOPTOSIS AND ITSBAX/BCL-2 IN THE KIDNEY TISSUE OFDIABETIC RATSObjectiveTo explore the changes of apoptosis in diabetic nephropathy and the effect of TZD on apoptosis in the kidney tissue of diabetic rats.Methods The animal model was induced by STZ.Wistar rats were randomly divided into following groups: normal control group(NC); normal control group with TZD(NCT) ;diabetic mellitus group(DM); DM group with TZD (DMT) .NCT and DMT were treated with TZD(3mg/kg.d) by gavage.The Bcl-2/Bax proteins of rats ronal tissue were detected by immunohistochemical methods(s-p).The apoptosis index of renal tissue was detected by the terminal deoxynucleotidyl transferase mediated nick end labeling, the ultrastructure of renal tissue was observed by electromicroscope in rats. Results Apoptosis index of diabetic group was significantly increased when compared with that of other three group (P<0.05).The expression of Bcl-2 protein and Bax protein in kidney tissue of each group werepresented in various degree. Pyknotic nuclei of mesangial cell, Which is the typical morphological features of apoptosis,were increased in kidney tissue of rats under eletromicroscope. Conclusions Both Bcl-2 and Bax proteins take part in the occurrence and progression of diabetic nephropathy.TZD can inhibit apoptosis of kidneys on diabetic rats through regulating the balance of expression of Bax/Bcl-2.It is one of the mechanism of TZD protective effect on diabetic kidney .PART THREEEFFECT OF TZD ON EXPRESSION OF P27KIP1/PCNAIN KIDNEY TISSUE OF DIABETIC RATSObjective To investigate the role of PCNA and p27Kip1in diabetic nephropathy,and the effects of TZD on the expression of PCNA and P27Kip1. Methods The animal model was induced by STZ.Wistar rats were randomly divided into following groups: normal control group(NC); normal control group with TZD(NCT) ;diabetic mellitus group(DM); DM group with TZD (DMT) .NCT and DMT were treated with TZD(3mg/kg.d) by gavage.P27kip1 mRNA expression was assessed by RT-PCR;The expression of PCNA and P27Kip1 protein was measured by immunohisto- chemical method. Results The expression of P27kip1 mRNA in among...