Effects Of Jiejufushenning On Expression Of Tumor Necrosis Factor-Alpha And Monocyte Chemoattractant Protein-1 And On Regulation Of PAI-1/tPA And TXB₂/6-k-PGF_1α In Rats Of Diabetic Nephropathy

PART ONE EFFECTS OF JIEJUFUSHENNING ON EXPRESSION OF TUMOR NECROSIS FACTOR-ALPHA AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN RATS OF DIABETIC NEPHROPATHYObjective:To investigate the effects of Jiejufushenning(JJFSN) on expression of tumor necrosis factor-alpha(TNF-α) and monocyte chemoattractant protein-1(MCP-1) in renal tissue and TNF-αlevel in serum of diabetic rats,explore its mechanism of renal protective effects.Methods:Diabetic SD rats were induced by intraperitoneal injection of streptozotocin,then the diabetic rats were randomly divided into three groups:diabetic control group(group B),Jiejufushenning group(group C), Irbesartan group(group D),age-matched healthy SD rats served as normal control group(group A).After 12 weeks of corresponding treatment,the fasting blood glucose(FBG),ratio of kidney weight and body weight,urea nitrogen,serum creatinine,and 24h urinary protein were detected by routine laboratory methods;TNF-αlevel in serum was detected by radioimmunoassay;TNF-αand MCP-1 in renal tissue were detected by immunohistochemical techniques.PAS stain was used to evaluate extracellular matrix(ECM)contents.The ultrastructure of renal tissue was observed under transmission electron microscope.Results:The fasting blood glucose(FBG),ratio of kidney weight and body weight,BUN,Scr,24huPro,serum TNF-αlevel,the expression of renal cortex TNF-αand MCP-1 were significantly increased in diabetic control group rats(p＜0.05).While the above indexes in JJFSN group, Irbesartan group were significant lower than those in diabetic control group(P＜0.05).The pathomorphism change of renal tissue in JJFSN group and Irbesartan group was also improved.Conclusion:JJFSN delays the progression of diabetic nephropathy in rats to some extent.These renoprotective effects are likely to be achieved through suppression of inflammatory factors such as TNF-αand MCP-1. PART TWO EFFECTS OF JIEJUFUSHENNING ON REGULATION OF PAI-1/tPA AND TXB₂/6-K-PGF_1α IN RATS OF DIABETIC NEPHROPATHYObjective:To investigate the effects of Jiejufushenning(JJFSN) on expression of plasminogen activator inhibitor-1(PAI-1) and tissue-type plasminogen activator(tPA) in renal tissue and on value of TXB₂/6-k-PGF_1α in urine of streptozocin induced diabetic rats.Methods:Diabetic SD rats were induced by intraperitoneal injection of streptozotocin,then the diabetic rats were randomly divided into diabetic control group and JJFSN group,age-matched normal SD rats served as normal control group.After 12 weeks of treatment by corresponding intervention,level of TXB₂ and 6-keto-PGF_1α in urine was detected by radioimmunoassay.Expression of PAI-1 and tPA in renal tissue were detected by immunohistochemical techniques.Results:The expression of renal cortex PAI-1,and value of TXB₂ and TXB₂/6-k-PGF_1α in urine were significantly increased in diabetic rats(p＜0.05),the expression of renal cortex tPA and the level of 6-k-PGF_1α in urine were decreased(p＜0.05),While the above indexes in JJFSN group were significantly improved than those in diabetic control group(P＜0.0 5).Conclusion:JJFSN exerts protective effect on renal histological feafures and renal function in STZ-induced DM rats,and its protective mechanism maybe related with the regulation of the balance of PAI-1/tPA in kidney and value of TXB₂/6-k-PGF_1α in urine.