| Objective1.Observe the effects of two methods of making model on renal injury in rats with chronic renal failure, and then establish an effective and consistent model of chronic renal failure in rats.2.Use the chronic renal failure model induced by the unilateral renal resection combined with tail repeated intravenous injection of adriamycin, and investigate the effects that BMSCs with artery transplantation treat chronic renal failure, and then analyze its influence and significance on kidney water channel protein、VEGF、 TGF-β1and renal ultrastructure, providing theoretical and experimental basis for clinical application that BMSCs transplantation treat chronic kidney disease.Methods1. The two ways of establishing animal model of chronic renal failure:(1) rat 5/6 nephrectomized (A group); (2) unilateral nephrectomy combined with repetition of tail vein injection of adriamycin (group B). Measure the rats’kidney function (blood urea nitrogen and creatinine), serum albumin, C-reactive protein (CRP)and observe the light microscope renal pathological changes in rats, comparing with normal rats (N group).2. The chronic renal failure rats built by unilateral nephrectomy combined with repetition of tail vein injection of adriamycin (ADR) were divided into three groups: normal group (N), the control group with Adriamycin (ADR group), MSCs with renal artery injection group (M-A group). Use immunohistochemistry method to detect the expressions of rat kidneys’ AQP1and AQP2,VEGF,TGF-β1and use X-electron microscopy to observe its ultrastructure, then test the kidney function,24h urine protein and serum albumin and serum sodium concentration respectively.Results1. The two kinds of modeling methods in group A and B rats had blood biochemistry and pathological changes, After 4,8,12 weeks, compared with N group, the other two groups of rats’ serum creatinine, urea nitrogen, CRP,increased significantly (P<0.01), but the Albumin decreased significantly (P<0.01). The difference of CRP from group A and B is statistically significant after 8 weeks (P 0.01). The rats from group A and B all have pathological changes under light microscope, glomerular and tubular renal interstitial were damaged. After 8 weeks, compared with group A, the extent and scope of renal interstitial inflammation pathological changes from group B is more obvious.2. ADR group, serum albumin concentration and 24h urine volume increased (P <0.01) M-A rats, serum sodium concentration and 24h urinary protein reduced (P <0.05), renal AQP1, AQP2 expression was significantly reduced (P<0.05;P<0.01), renal VEGF expression was significantly increased (P<0.01),renal TGF-01 expression was prominently reduced (P<0.01), renal ultrastructure in rats in ADR group presented degeneration, BMSCs transplantation improves its ultrastructure.Conclusions1. CRF rat model established in two ways, the results met the requirements of the CRF model, increased blood urea nitrogen and creatinine significantly; horizontal comparison model created in two ways renal dysfunction and malnutrition, the effect is much the same.2. Compared with chronic renal failure induced by 5/6 nephrectomy model, the model induced by the unilateral renal resection combined with tail repeated intravenously injection of adriamycin, micro-inflammatory state appear earlier, renal interstitial inflammation changes pathologically quicklier.3.The same kind of bone marrow mesenchymal stem cells transplantation is safe, and there are portable therapeutic prominently effect in the renal tubular repair.4.BMSCs transplantation is able to reduce urine albumin excretion in rats, increase serum albumin levels, reduce blood sodium levels, reduce water and sodium retention, improve kidney local micro-circulation of renal tissue fibrosis, promote the repair of renal function, which is the bone marrow mesenchymal stem cells transplantation down AQP1, AQP2 over-expressions, inhibit the synthesis of TGF-pβ1 in the kidney of local and increase the over-expressions of renal VEGF. |
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