Font Size: a A A

Intervention Study Of Zhenhuaxiaoshen Capsule In Experimental Diabetic Rat Podocyte EMT Wnt/Beta-catenin Pathway

Posted on:2014-11-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:S J SunFull Text:PDF
GTID:1264330425967120Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Propose: Diabetic nephropathy (DN) is a common and serious diabetic complication ofblood vascular. The main features of DN are proteinuria and renal function changes.The mainpathological changes are glomerular filtration change, thickening of the basement membrane,mesangial cells widened, glomerular sclerosis, until the renal failure. Its high incidence andfast progress is a serious threat to human health.The pathogenesis of diabetic nephropathy is more complex. In recent years, for the pointof view of the mechanism of proteinuria, podocyte has become a hot research. All factorsinjury podocyte will be involved in proteinuria, so the drug for improving podocyte functionbecomes hot spot and innovation in treatment of diabetic nephropathy. For the treatment ofdiabetic nephropathy proteinuria, Western medicine mainly adopt degraded blood glucosedrugs, ACEI/ARB drugs, improving circulatory drugs, until dialysis therapy whenintermediate stage or advanced stage. And traditional Chinese medicine in the treatment ofproteinuria has fine effective, which the western medicine can not be matched.ZhenHuaXiaoShen capsule my advisor commonly used is a prescription in the treatment ofdiabetic nephropathy proteinuria, which achieves satisfactory effect in clinical patients. Thisexperiment observes the influence of podocyte correlated molecules and podocyte EMT inwnt/β-catenin signal transduction pathway by ZhenHuaXiaoShen capsule interventionexperimental diabetic rats. And further evidence of ZhenHuaXiaoShen capsule for thetreatment of diabetic nephropathy proteinuria is effective.Method:1Wistar rats being feed with hypsi-lipoids feeder for a month has been intraperitonealinjected with streptozotocin (STZ) for making diabetic rat model. The successful DM rats arerandomly divided into DM model group, the experimental group with traditional Chinesemedicine, the control group with western medicine, and normal control group.ZhenHuaXiaoShen capsule has been used in the experimental group, while rosiglitazone andbenazepril has been used together in the control group. Observed rats the general state, testingthe blood glucose, blood lipids, renal function, urine output and urine micro albumin.2Observed renal ultrastructure by optical microscope and perspective electronmicroscopy, and analyzed the renal organism pathological structure changes for ZhenHuaXiaoShen capsule intervention experimental diabetic rats.3Observed the protein expression of podocyte signal molecule,like nephrin, desmin,zo-1by immunohistochemical method, and m RNA expression of nephrin, desmin byfluorescent quantitative PCR methods.4Observed the protein expression of podocyte EMT related molecules, like wnt-1、β-catenin、snail1in wnt/β-catenin signal transduction pathway by immunohistochemicalmethod, and m RNA expression of wnt-1, snail1by fluorescent quantitative PCR.Result:1ZhenHuaXiaoShen capsules can improve the experimental DM rats the general stateand clinical symptoms, such as polydipsia, polyphagia, polyuria and athrepsy.2ZhenHuaXiaoShen capsules can degrade the experimental DM rats blood glucose,triglyceride, cholesterol in a certain degree, and improve glycometabolism and lipidmetabolism.3ZhenHuaXiaoShen capsule can inhibit the experimental DM rats the early renalhypertrophy, reduce urinary albumin discharge, degrade serum creatinine and blood ureanitrogen, improve renal function.4ZhenHuaXiaoShen capsules improve the experimental DM rats nephridial tissuepathology, reduce the thickening of the glomerular basement membrane, extracellular matrixaccumulation, mesangial hyperplasy, improve podocyte morphous, thereby reducing DMglomerulosclerosis.5ZhenHuaXiaoShen capsule can inhibit the experimental DM rats nephridial tissueprotein and m RNA expression of nephrin and zo-1, increase protein and m RNA expressionof desmin.6ZhenHuaXiaoShen capsule can inhibit the experimental DM rats nephridial tissueprotein and m RNA expression of wnt-1, β-catenin and sail1in wnt/β-catenin signaltransduction pathway.Conclusion:ZhenHuaXiaoShen capsules can improve the experimental DM rats the general state andclinical symptoms of polydipsia, polyphagia, polyuria and athrepsy; inhibit the early renalhypertrophy and relieve the renal pathological structure; degrade blood glucose, triglyceride,cholesterol, reduce urinary albumin discharge, degrade serum creatinine and blood urea nitrogen. ZhenHuaXiaoShen capsules can also improve podocyte correlated proteinexpression of nephrin, zo-1and desmin, inhibit the expression of wnt-1, β-catenin and sail1in podocyte EMT in wnt/β-catenin signal transduction pathway. Therefore,ZhenHuaXiaoShen capsules can improve glycometabolism and lipid metabolism, reduceurine protein, and protect renal function by the way of intervention in podocyte EMT in wnt/β-catenin signal transduction pathway.My advisor NanZheng professor considers that the pathogenesis key of diabeticnephropathy is poison damaged renal meridian and hidden in pleurodiaphragmatic spaces.Creatively associate two theory of the traditional Chinese medicine theory of poison damagedrenal meridian and hidden in pleurodiaphragmatic spaces and western medicine diabeticnephropathy pathogenesis, glomerular filtration membrane-structure and function ofpodocytes together. ZhenHuaXiaoShen capsule could treat diabetic nephropathy in the way ofdetoxification-deoppilation meridian and pleurodiaphragmatic spaces-tonifying kidney-eliminate pathogen by intervention podocyte EMT in wnt/β-catenin signal transductionpathway.
Keywords/Search Tags:ZhenHuaXiaoShen capsule, podocyte, EMT, signal transduction pathway
PDF Full Text Request
Related items