| Objective: Diabetic nephropathy is not only a serious chronic implication of diabetes ,but also an important factor which leads to chronic renal failure.Many studies have showed that plasminogen activitor inhibitor-1 (PAI-1) may be an important role in the diabetic nephropathy,which is often associated with synthesis and degradation disturbance of collagen IV.Puerarm is one of the Chinese herbs.It has an inhibitory effect on the fast and slow non-enzymatic glycation reaction .The non-enzymatic glycation end products(AGEs) have effect on the expression and bioactivity of PAI-1,and promote the synthesis of collagen IV.Valsartan,the angiotensin type 1 recepter antagonist,has some renal protective effect on diabetes.In this study,firstly we developped the type 2 diabetic rat by high-sucrose-high-fat diet and a low dose of STZ was injected to them,then examed PAI-1 bioactivity in plasma and the protein expression of PAI-1 and collagen IV to discuss the protection of Puerarin in the rat kidney and offer the bases for clinical treatment of DN.Methods: The SD rats were fat-fed for one month,thengiven STZ 30mg/kg intraperitoneally. 2 weeks later,blood glucose and serum insulin levels were measured. The rats with blood glucose levels greater than 7.8mmol/L and insulin sensitivity decresed were considered as diabetes.Those were randomly divided into following groups:normal control rats(group A),diabetic rats(group B),diabetic rats treated with Valsartan(group C), diabetic rats treated with Puerarin(group D). Plasmin glucose, insulin, serum cholesterol, serum triglyceride and creatinine ,urinary albumin were observed after treatment .PAI-1 bioactivity in plasma and protein express of PAI-1 and collagen IV were measured by immunhistological staining . One kidney was taken for morphological study. Results were analysed by HPIAS-1000 computer image-analysis system,The rate of positive for collagen IV and ILD of PAI-1 in the rat renal cortex were counted.Results: 1.blood glucose,serum insulin and serum lipids:Insulin levels of group B and C and D rats increased in response to the high-sucrose and high-fat diet and insulin resistance was confirmed.After STZ injection, hypergly-cemia(16.21+7.80mmol/L vs 5,70+0.89mmol/L in controls, P<0.05) was observed,and plasma insulin decreased to levels of chow-fed rats with hypertriglyceridemin and hyper-cholesterolemia.2. PAI-1 bioactivity in plasma and renal cortex : In group B,PAI-1 bioactivity in plasma and renal cortex 0.98+0.43AU/ml,1.04±0.22AU.(mg.Pr)-1 were increased signifi?cantly than that of the control 0.42±0.11AU/ml,0.37±0.13 AU.(mg.Pr)-1 (both P<0.01) The rats of group C 0.57 + 0.17AU/ml,0.60 ±0.14 AU.(mg.Pr)-1 were lower than group B (both P<0.05) .In group D,they were also decreased than that of group B 0.60±0.14AU/ml,0.65± 0.17AU.(mg.Pr)-' (both PO.05) ,But there was no difference between group C and D (P>0.05) .3. the protein expression of collagen IV and the ILD of PAI-1: In group B,the protein expression of collagen IV 35.98±4.35(%)was higher than that of the control 8.30 + 0.76(%), The group C and D were lower than group B 10.71 +0.70(%)>12.53 + 0.89(%) (both PO.01) .The ILD of PAI-1 in group B was elevated(0.569 + 0.055),It was decreased in group C and D 10.71 +0.70(%), 12.53 + 0.89(%) than group B ( both P<0.01 ) .There was a positive correlation between PAI-1 and collagen IV (r=0.791 , P0.01) .4. renal function and urinary Alb.BUN (P<0.01 X Scr (P<0.01 ) Alb (P<0.05 ) in group B were elevated than thatof the control.Those of group C and D were lower than group B (PO.05 > PO.01 > P0.05 ) .But between group C and D,no difference were found. Ccr was decreased in group B (P0.01) ,but elevated in group C and D (both P0.01)5. serum lipids:TC,TG,LDL and VLDL in group B were elevated than that of the control (all PO.05 ),Those of groupC and D were lower than group B(all P<0.05 ),HDL in group B was decreased (P<0.01) ,but increased in group C and D (bothP<0.01)6. The morphological ex... |
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