| Diabetic nephropathy is a major long-term microvascular complication of diabetes mellitus. Morphologically, the early lesion is renal hypertrophy due to the disturbance of cell cycle. The development of diabetic nephropathy is characterized by progressive thickening of glomerular basement membrane and by expansion of the mesangial extracelluar matrix (ECM), which finally leads to glomerulosclerosis. The onset of diabetic nephropathy is a result of combined action of multiple factors, including glucose metabolism disturbance, altered glomerular hemodynamics, as well as production and release of cytokine factors and growth factors. The transforming growth factor- β1 (TGF- B 1) and nephrin have been implicated as an important factor in pathogenesis of diabetic nephropathy. TGF- β1 has been reported to promote synthesis of ECM components, which leads to glomerular hypertrophy, the thickeness of GBM, ECM accumulation and glomerulosclerosis. Indirect and direct evidences have indicated that nephrin, a recently identified main protein of the glomerular slit-diaphgram, acts as maintenace the integrity of the stucture andfuction on the glomerular slit-diaphgram. Its defienciency and abnormal distribution may reduce to protein urine.VCR is a kind of cellcycle special drug , it can inhibitate the proliferation of cell. We use VCR to treat tumor clinically. But we find that it can reduce the protein urine on the nephrotic syndrom patients. Sowe conclude that it may be used on diabetic nephropathy.TO testify the treatment effect of vincristine on diabetic nephropathy rat, STZ was used to induce the diabetic nephropathy models of rat. We devided the models into three groups: the normal contral group, the model group and the treatmrnt group. The treatment group was treated with vincristine through tail vein, 0.2mg/kg, twice a week. The research methods employed in the present study included biochemistry method, the renal morphological changes, immunohistochemical analysis, Western blot, reverse transcription polymerase chain reaction (RT-PCR). The parameters evaluated included: (l)the blood glucose,urinary protein, the renal fuction,the ratio of kidney weight to body weight. (2) the renal tissue was observed by light microscopy and electronic microscopical examination. (3) TGF-/31 mRNA expression in the cortex of rat kidney. (4) the expression of nephrin protein in rat kidney.The main results were as follows:1 .The biochemical analysis and the morphorlogical change in the DN rat is similar to those in human. Histologically, mesangial cell proliferation and ECM deposition were found in the rats with injection of STZ. Electron microscopical examination showed glomerular basement membrane segmentally thickened, podocyte widely fused, mesangialmatrix excessively deposited in the rats treated with STZ.2.1mminohistochemical examination revealed that the strongimmulogical staining of TGF-β1 in glomeruli of rats injected with STZ.TGF-β1 mRNA expression was significantly increased in this group.3.Nephrin protein production were down-regulated in renal cortex of ratafter STZ administration for 12weeks.4.VCR can reduce the urinary protein excretion in STZ induced rat. Itcan reduce the ECM deposition, glomerular basement membranethickeness and podocyte fusion.5.VCR can reduce the intensity of immulogical staining and mRNAexpression of TGF-β1 in glomeruli of rats injected with STZ.6. VCR can increase the nephrin protein product in the cortex of STZrat.The main conclusions are: 1 .The biochemical analysis and the morphorlogical change in the DN ratis similar to those in human.2. VCR can reduce the urinary protein excretion in STZ induced rat. Itcan be relatated with the increasion the nephrin protein product.3.The ratio of kidney weight to body weight is increased in STZ rat, sowe can draw a conclusion that renal hypertrophy exist in the early stageof DN.4.VCR can reduce the ECM deposition, glomerular basement membranethickeness and podocyte...
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