Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Chin Med J (Engl). 2009 Nov 5;122(21):2573-9.
Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells (MSCs) transplantation could attenuate diabetic nephropathy in experimental diabetic rats.
Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Diabetic rats were randomized to four groups: diabetes control group (DC), ciclosporin A group (CsA), MSC group, and MSC + CsA group (MSCA). Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1, 2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio (Alb/Cr), endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined.
Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group (P < 0.05, respectively). The Alb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group (P < 0.05). And the Alb/Cr in MSCA group showed a significant decrease compared with MSC group (0.74 vs 0.84, P < 0.05). There was a significant difference in renal mass index between the MSCA group and DC group (5.66 vs 6.37, P < 0.05). No significant difference was found in creatinine clearance rate among 4 groups (P > 0.05). Treatment with MSC + CsA significantly ameliorated the morphology of diabetic kidney.
MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, Alb/Cr ratio and renal mass index.
糖尿病肾病是糖尿病的常见并发症。本研究旨在探讨骨髓间充质干细胞（MSCs）移植是否能减轻实验性糖尿病大鼠的糖尿病肾病。
Sprague-Dawley 大鼠单次腹腔注射链脲佐菌素（STZ）（60mg/kg）。糖尿病大鼠随机分为四组：糖尿病对照组（DC）、环孢素 A 组（CsA）、MSC 组和 MSC+CsA 组（MSCA）。体外通过 5-溴-2'-脱氧尿苷（BrdU）培养、鉴定和标记骨髓间充质干细胞。然后通过心内输注将其移植到糖尿病大鼠体内。每天给予环孢素 A 5mg/kg。移植后 1、2、4、8 周，检测随机血糖、尿白蛋白/肌酐比值（Alb/Cr）、内源性肌酐清除率和肾质量指数。检查肾脏形态和标记细胞。
培养的 MSCs 表达间充质细胞表型，并能向成骨细胞和脂肪细胞多向分化。在肾病大鼠的肾脏中可以检测到标记的 MSCs，主要在肾间质中，但在肾脏中植入后没有增殖。在整个实验过程中，MSCA 组与 MSC 组、CsA 组和 DC 组相比，血糖明显下降（分别 P<0.05）。MSCA 组和 MSC 组的 Alb/Cr 明显低于 CsA 组和 DC 组（均 P<0.05）。而且 MSCA 组与 MSC 组相比 Alb/Cr 明显下降（0.74 比 0.84，P<0.05）。MSCA 组与 DC 组的肾质量指数差异有统计学意义（5.66 比 6.37，P<0.05）。4 组间肌酐清除率差异无统计学意义（P>0.05）。MSC+CsA 治疗明显改善了糖尿病肾病的形态。
MSC 通过降低血糖、Alb/Cr 比值和肾质量指数，轻度改善糖尿病肾病。
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