骨髓间充质干细胞移植改善糖尿病肾病大鼠血糖及尿总蛋白

Transplantation of bone marrow mesenchymal stem cells to improve blood glucose and urinary total protein levels in diabetic nephropathy rats

背景：糖尿病肾病防治的基本措施包括有效控制血糖、控制血压、抑制肾素-血管紧张素系统和调脂治疗等,但往往无法获得理想的效果。目的：探讨骨髓间充质干细胞移植糖尿病肾病大鼠的血糖及尿总蛋白改善情况。方法：45只SD大鼠随机分为3组,每组15只,分别设为正常对照组、糖尿病肾病组和干细胞移植组。糖尿病肾病组和干细胞移植组一次性腹腔注射链脲佐菌素60 mg/kg制备糖尿病肾病模型,正常对照组注射相同剂量的柠檬酸-柠檬酸钠缓冲液,造模后将2×10^6（200μL）骨髓间充质干细胞直接注射到干细胞移植组大鼠左心室,首次移植后7 d进行第2次移植。正常对照组和糖尿病肾病组心内注射相同剂量的无血清L-DMEM培养基。治疗后1,4,8周检测3组大鼠的尿总蛋白和血糖。结果与结论：①治疗后1,4,8周：干细胞移植组以及糖尿病肾病组的血糖及尿总蛋白水平均显著高于对照组（P〈0.05）。②治疗后1周：干细胞移植组血糖及尿总蛋白水平显著低于糖尿病肾病组（P〈0.05）。③治疗后4,8周：糖尿病肾病组血糖及尿总蛋白水平稍高于干细胞移植组,但差异无显著性意义（P〉0.05）。④实验结果表明,骨髓间充质干细胞移植治疗糖尿病肾病大鼠可以在短时间内获得良好的治疗效果,显著改善大鼠的血糖及尿总蛋白水平,但长期治疗效果不佳。

BACKGROUND： Common strategies for preventing diabetic nephropathy include effective control of blood sugar and blood pressure, inhibition of the rennin-angiotensin system and lipid-lowering therapy, but it is often difficult to get the desired results. OBJECTIVE： To investigate the effect of transplantation of bone marrow mesenchymal stem cells on levels of blood glucose and urinary total protein in diabetic nephropathy rats. METHODS： Forty-five Sprague-Dawley rats were randomly divided into three groups（n=15 per group）： normal control group, diabetic nephropathy group and stem cell transplantation group. Rats in the diabetic nephropathy and stem cell transplantation groups were given single use of 60 mg/kg streptozotocin to make diabetic nephropathy models. The same dose of citric acid-sodium citrate buffer was injected in the normal control group. After modeling, 200 μL of bone marrow mesenchymal stem cell solution（2×10^6） was injected into the left ventricle of rats in the stem cell transplantation group, and then at 7 days after the first transplantation, the cell transplantation was conducted again. The same dose of serum-free L-DMEM was injected intracardially into the rats in the normal control and diabetic nephropathy groups. Levels of urinary total protein and blood glucose were detected. RESULTS AND CONCLUSION： At 1, 4, 8 weeks after treatment, the urinary total protein and blood glucose levels were significantly higher in the stem cell transplantation group and diabetic nephropathy group than the normal control group（P〈0.05）. At 1 week after treatment, the urinary total protein and blood glucose levels were significantly lower in the stem cell transplantation group than the diabetic nephropathy group（P〈0.05）. At 4 and 8 weeks after treatment, the total urinary protein and blood glucose levels were slightly higher in the diabetic nephropathy group than the stem cell transplantation group, but there was no significant difference（P〉0.05）. These findings indicate that bone marrow mesenchymal stem cell transplantation in diabetic nephropathy rats can get good results in a short period, significantly improve the blood glucose and urinary total protein levels, but the long-term treatment effect is poor.