| Chronic kidney disease is commonly encountered. It induces chronic renal failure and injury of multiple organs in fine. But it is not effectively treated. Recent years,stem cells transplantation therapy for kidney diseases was generally studied. More and more evidence certified effect of stem cells transplantation on acute kidney injury. But the study on stem cells transplantation therapy for chronic kidney injury was seldom reported. Moreover,the effect was not positive. We builded the model of subtotal nephrectomized rats and injected bone marrow mononuclearcells and human umbilical cord mesenchymal stem cells into heart of subtotal nephrectomized rats. Then we researched protective effect and molecular mechanism.Objective To build the model of subtotal nephrectomized rats,study the effect of bone marrow mononuclearcells and human umbilical cord mesenchymal stem cells on glomerulosclerosis and expression of TGF-β1, CTGF and TIMP-1 in subtotal nephrectomized rats. To approach the effect of stem cells transplantation and mechanism.Methods After successfully building model of subtotal nephrectomized rats,rats were divided into control group,not treated glomerulosclerosis group(NT) , bone marrow mononuclear cells treated glomerulosclerosis group(MT1) , human umbilical cord mesenchymal stem cells treated glomerulosclerosis group(MT2) and mixed treated glomerulosclerosis group(MT3). The rats in the latter four groups were subjected to subtotal nephrectomy. The bone marrow mononuclear cells treated group was injected bone marrow mononuclear cells into heart at a dose of 1.0×10~8,the human umbilical cord mesenchymal stem cells treated group was injected human umbilical cord mesenchymal stem cells at a dose of 1.0×10~5,the mixed treated group was injected the both cells at the half dose. 4 weeks later,urine protein excretion,urea nitrogen and creatinine were measured. Then the rats were sacrificed and the left kidney was subjected to pathological evaluation. The expression of TGF-β1,CTGF and TIMP-1 was measured.Results 1. Urine protein excretion and renal function: Compared with the NT group,MT1,MT2 and MT3 groups showed lower urine protein excretion,urea nitrogen and creatinine level. Except urea nitrogen of MT3 group was not statistical significance compared with NT group,urine protein excretion and renal function of stem cells group were statistical significance(P<0.05). But among MT1,MT2 and MT3 groups urine excretion and renal function were not statistical significance(P>0.05). 2. Pathology analysis of nephridial tissue: Compared with NT group,glomerulosclerosis and renal interstitial fibrosis in MT1,MT2 and MT3 groups were slighter,comparative areas of glomerular matrix and glomerulosclerosis index were lower(P<0.05). But among MT1,MT2 and MT3 groups pathology changes of nephridial tissue were not statistical significance(P > 0.05). Electron microscope ultra-structure showed slighter ingury compared with the NT group in podocyte. 3.The immunohistochemical staining results: There was some expression of TGF-β1 and TIMP-1 in glomerular epithelial cells and tubular epithelial cells of C group. There was expression in glomerular mesangial cell,epithelial cells, mesangial region and tubular epithelial cells of NT group. Compared with the NT group,MT1,MT2 and MT3 groups showed lower expression of TGF-β1 and TIMP-1(P<0.05). But among MT1,MT2 and MT3 groups expression of TGF-β1 and TIMP-1 was not statistical significance(P>0.05). 4. The western blot results: Compared with NT group,MT1,MT2 and MT3 groups showed lower expression of TGF-β1 and CTGF(P<0.05). But among MT1,MT2 and MT3 groups expression of TGF-β1 and CTGF was not statistical significance(P>0.05).Conclusion Bone marrow mononuclearcells and human umbilical cord mesenchymal stem cells can decrease urine protein excretion,blood urea nitrogen and creatinine level,and it can protect renal function in subtotally nephrectomized rats. Morphology study showed that bone marrow mononuclearcells and human umbilical cord mesenchymal stem cells can inhibit glomerular hypertrophy,decrease glomerulosclerosis areas,renal interstitial fibrosis and podocyte ingury.Expression up-regulation of TGF-β1,CTGF and TIMP-1 in subtotal nephrectomized rats breaked the balance of extracellular matrix and nephrosclerosis. Bone marrow mononuclearcells and human umbilical cord mesenchymal stem cells can decrease expression of TGF-β1,CTGF and TIMP-1 in nephridial tissue,decrease nephrosclerosis and protect the kidney.
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