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The Effects Of Self-made Bao'shen Recipe On Expressions Of CTGF And MMP-9 In Experimental Diabetic Nephropathy Rats

Posted on:2010-02-09Degree:MasterType:Thesis
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:2144360275495987Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Diabetic nephropathy is a serious cap vascular complication of diabetes.It is a very important cause bringing about the terminal stage of nephropathy.The pathogenesis of diabetic nephropathy is not clear.It is generally considered that it is interrelated with the synergy of Hyperglycemia,metabolic disturbance of polylol-phaseomannite,oxidizes stress,abnormality of hemodynamics,abnormality of zymoplastic mechanism,nonenzymatic promoted glycosylation.The accumulation of extracellular matrix is one of the important pathologic changes of diabetic nephropathy.Now,TGF-β1 and CTGF are considered to be one of the important driver molecules for ECM accumulation in the pathogenesis of diverse forms renal fibrosis including glomerulosclerosis in diabetic nephropathy,and may constitute a more specific target for futuramic anti-fibrosis therapies.It is very important to keep the function of inflammatory reaction.It can influence the formation of extracellular matrix(ECM),which includes inducing synthesis of various matrix proteins,inhibiting expression of ECM degradation enzyme,disturbing synthesis and decomposition of ECM,and leading to excessive accumulation of ECM,which result in glomerulosclerosis at last.It was found that CTGF played a key role in the occurrence and development of diabetic nephropathy.CTGF is the downstream medium of transforming growth factor-β1(TGF-β1),but CTGF does not involve in the resisting proliferation and inflammation function of TGF-β1,and only involve in accelerating cell matrix synthesis function of TGF-β1.CTGF can induce mesangial cells and other renal resident cells producing ECM by autocrine and paracrine,thereafter accelerate the glomerular hypertrophy and glomerulosclerosis inevitably.Matrix metalloproteinases are mainly play degradation of extracellular matrix. Matrix metalloproteinases-9 say again gelatinases B,which is one of the main members of the family of MMPs.Ⅳ,Ⅴ,Ⅶ,Ⅹtype collagen,gelatin and elastic fiber are the substrate.MMP-9 in the form of enzyme secretion,must be activated to degrade matrix collagen and other proteins.Generally considered fibrinolytic enzyme in fibrinolytic enzyme activator activation is under the action of fibrinolytic enzyme, the latter to cascade amplification waterfall effect MMP-9 to activate substrate biodegradation.The intraperitoneal injection of streptozotocin was conducted to made models of diabetic rats within a short period of time and impairment of diabetic nephropathy occurred after that.This article aims at discuss the expressions of CTGF and MMP-9 at the early stage of diabetic nephropathy and the mechanism of the curative effects of self-made Bao'shen recipe on diabetic nephropathy.Objective:The study use Bao'shen recipe to intervent diabetic rats and detect the expression level of CTGF and MMP-9 of renal tissue in control group,diabetic rat group and Bao'shen recipe treating diabetic rat group by immumohistochemistry way. In addition,in order to provide theoretical basis for the treatment of DN and the possible mechanism of protecting kidney,we have detected the clinical and metabolic parameters of this three groups.Methods:Wistar rats were randomized divided into control group,diabetic rat group and Bao'shen recipe treatment group.The control group received intraperitoneal injection with citric acid buffer solution.STZ was injected through abdominal cavity to make models of diabetic rats.Bao'shen recipe treatment group was set up based on models of diabetic rats with feeding Bao'shen recipe.Blood, urine and renal tissue were obtained after 8 weeks.Blood glucose,cholesterol,urea nitrogen,serum creatinine,24 hour-urinary albumin,weight of kidney,body weight and the pathological changes of kidney tissues were measured.Technique of immunohistochemistry was also taken to measure the expression of CTGF and MMP-9 in this three groups.Result:Compared with group C,expressions of CTGF were higher[(0.234±0.009) vs(0.146±0.007),P<0.01],while the expressions of MMP-9 were lower[(0.146±0.006) vs(0.236±0.007),P<0.01]in renal tissue of group D. Kidney hypertrophy index,24-hour urinary protein,blood glucose,cholesterol,urea nitrogen and serum creatinine increased significantly in the group D.The level of MMP-9 expression was advanced[(0.175±0.007) vs(0.146±0.006),P<0.01],while the level of CTGF expression was reduced[(0.194±0.008) vs(0.234±0.009),P<0.01] by using Bao'shen recipe.In group DB,kidney hypertrophy index,24-hour urinary protein,cholesterol,urea nitrogen and serum creatinine obviously lower than diabetic rat group.Conclusion:Self-made Bao'shen recipe can depress the expressions of CTGF and increase the expressions of MMP-9 in the kidney of diabetic rats,as a result, which can be served as a protective effect to prevent progress of diabetic nephropathy.
Keywords/Search Tags:Traditional Chinese drug, Diabetic nephropathy, Connective tissue growth factor, Matrix metalloproteinase-9
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