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骨髓间充质干细胞治疗大鼠糖尿病肾病

[Bone marrow mesenchymal stem cell therapy on diabetic nephropathy in rats].

作者信息

Zhou Hong, Gao Yun, Tian Hao-Ming

机构信息

Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Nov;40(6):1024-8.

Abstract

OBJECTIVE

To test the effectiveness of bone marrow mesenchymal stem cell (MSC) transplantation on diabetic nephropathy in rats.

METHODS

A single intraperitoneal injection of STZ (60 mg/kg) was given to Sprague-Dawley (SD) rats. Four weeks after the occurrence of diabetes, the rats with diabetic nephropathy were randomly divided into two groups: diabetic nephropathy control group (DN, n = 12) and MSCs transplantation group (MSC, n = 12). Six rats served as normal controls. MSCs were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro, which were then transplanted to the rats in the MSC group via introcardiac infusion(2 x 10(6) MSCs/200 microL). The same procedure was repeated one week later. The blood glucose, body weight (BW), kidney weight (KW), urine protein, endogenous creatinine clearance rate (Ccr) and profile of kidney hypertrophy (KW/BW) were tested and the renal morphology and labeled cells were examined in the kidney, one, two, and eight weeks after the second transplantation.

RESULTS

Mesenchymal cell phenotype was expressed by the cultured MSCs, which could be multidifferentiated into osteogenic and adipogenic cells. The labeled MSCs were detected in the kidney of nephropathic rats, but no proliferation of the stem cells was found. The rats in the MSC and DN groups had higher blood glucose, urine protein, Ccr and KW/BW and lower BW than the normal controls (P < 0.05). One week after the transplantation, the rats in the MSC group showed lower blood glucose than the rats in the DN group [(26.7 +/- 2.8) vs (29.9 +/- 1.6) mmol/L, P < 0.05], but was still higher than the normal controls (6.0 +/- 0.7 mmol/L). The urine protein appeared similar in the MSC and DN groups two weeks and eight weeks after transplantation. After two weeks of transplantation, the rats in the MSC group showed lower Ccr (8.6 +/- 1.9) and KW/BW (5.5 +/- 0.1) than the rats in the DN group (17.1 +/- 1.6 for Ccr and 6.2 +/- 0.3 for KW/BW respectively, P < 0.05).

CONCLUSION

Cardiac injected bone marrow mesenchymal stem cells can track to the kidney of rats with diabetic nephropathy, which attenuates diabetic nephropathy temporarily.

摘要

目的

检测骨髓间充质干细胞(MSC)移植对大鼠糖尿病肾病的疗效。

方法

对Sprague-Dawley(SD)大鼠单次腹腔注射链脲佐菌素(STZ,60 mg/kg)。糖尿病发生四周后,将糖尿病肾病大鼠随机分为两组:糖尿病肾病对照组(DN,n = 12)和MSC移植组(MSC,n = 12)。六只大鼠作为正常对照。体外培养、鉴定并通过5-溴-2'-脱氧尿苷(BrdU)标记MSC,然后经心内输注(2×10⁶个MSC/200 μL)将其移植到MSC组大鼠体内。一周后重复相同操作。在第二次移植后的1周、2周和8周检测血糖、体重(BW)、肾脏重量(KW)、尿蛋白、内生肌酐清除率(Ccr)和肾脏肥大指标(KW/BW),并检查肾脏的形态和标记细胞。

结果

培养的MSC表达间充质细胞表型,可多向分化为成骨细胞和脂肪细胞。在肾病大鼠的肾脏中检测到标记的MSC,但未发现干细胞增殖。MSC组和DN组大鼠的血糖、尿蛋白、Ccr和KW/BW均高于正常对照组,而BW低于正常对照组(P < 0.05)。移植后1周,MSC组大鼠的血糖低于DN组[(26.7±2.8) vs (29.9±1.6)mmol/L,P < 0.05],但仍高于正常对照组(6.0±0.7 mmol/L)。移植后2周和8周,MSC组和DN组的尿蛋白相似。移植2周后,MSC组大鼠的Ccr(8.6±1.9)和KW/BW(5.5±0.1)低于DN组(Ccr分别为17.1±1.6,KW/BW为6.2±0.3,P < 0.05)。

结论

经心内注射的骨髓间充质干细胞可追踪至糖尿病肾病大鼠的肾脏,可暂时减轻糖尿病肾病。

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