| Objective To investigate the effectiveness of bone marrow mesenchyrnal stem cell (MSC) and different transplantation methods of MSC on adriamycin (ADR) model of nephropathy in rats. Methods The ADR model of nephropathy was induced by left nephrectomy plus injection of ADR (2.5mg/kg) in Sprague-Dawley (SD) rats, once a week for two weeks. The model rats with nephropathy were randomly divided into three groups:adriamycin nephropathic model control group (ADR, n=12), MSCs transplantation through right renal artery group (M-A,n=12) and MSCs transplantation through peripheral veins group (M-V, n=12). Another12SD rats were served as normal controls (Sham, n=12). MSCs were cultured,transplanted via right renal artery (2×106/mL) to rats in M-A group, and were transplanted via peripheral veins2×106/mL)to rats in M-V group. The same procedure was repeated in two weeks. The blood urea nitrogen, serum creatinine,24h urine protein and24h urine output,hemoglobin,serum albumin,serum sodium level were detected before transplantation and in one and two weeks after the second transplantation. The renal morphology and labeled cells were examined in the kidney one week after the second transplantation. Results The values of blood urea nitrogen, serum creatinine,24h urine protein and serum sodium level were significantly higher in M-A group, M-V group and ADR group than those of Sham group (P<0.01). The values of hemoglobin,serum albumin,24h urine output were significantly lower in M-A group, M-V group and ADR group than those of Sham group (P<0.01).The level of hemoglobin was significantly higher before the second transplantation in M-A group than that of ADR group (P<0.01). The serum level of creatinine was significantly decreased in M-A group than that of ADR group and M-V group (P<0.01). The levels of24h urine protein were significantly lower after one week transplantation in M-A group than those of MV group (P<0.01). The levels of hemoglobin were significantly higher after one week transplantation in M-A group than those of MV group (P<0.01),but no significant differences in the levels of urine protein and hemoglobin between M-A group and M-V group.The kidney organization structure stained by HE were observed under the optical microscope after the MSCs transplanted:the renal glomerular,the renal tubules and the renal interstitium of Sham group had no obvious pathological changes;The glomerular mesangial cells and extra cellular matrix appeared different sizes of hyperplasia in the ADR group. There were glomerular focal segmental sclerosis, renal interstitial flake fibrosis and a large number of inflammatory cells infiltration;The glomerular mesangial cells and extra cellular matrix appeared different sizes of hyperplasia in the M-V group. There were visible focal renal interstitial fibrosis and inflammatory cell infiltrating;In the M-A group,most of the glomerular capillary loop had expansion. The renal tubules had no obvious atrophy. There were few inflammatory cells infiltrating and the renal interstitial fibrosis were not obvious. After the MSCs transplanted on the1st day,the7th day,the14th day and the30th day, Sham group showed little green fluorescent display under the confocal fluorescence microscope in each point time; ADR group showed almostly no green fluorescent display; In the M-V and M-A group we could see green fluorescent display on the first day. The green fluorescent was the strongest on the14th day.But after30days it decreased significantly. In the M-V group,the fluorescence distributed only in the renal tubules.In the M-A group,the fluorescence distributed not only in the renal tubules but also in the. glomerulus. Conclusion Transplantation of MSCs can alleviate renal damage of chronic ADR-induced nephropathy, which is more effective in rats with MSCs transplantation via renal artery than that in rats with MSCs transplantation via peripheral vein which would provide a better theoretical basis for future clinical application. |
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