骨髓干细胞在小鼠糖尿病性肾脏疾病表型转移中的作用

The role of bone marrow stem cells in the phenotype transfer of diabetic kidney disease

目的观察骨髓干细胞在糖尿病性肾脏疾病表型转移中的作用。方法采用链脲佐霉素(STZ)腹腔注射复制糖尿病动物模型,分离糖尿病小鼠和正常小鼠骨髓细胞,经尾静脉分别注入受放射后的小鼠体内作为实验组及对照组,移植后第8周测定各组小鼠空腹血糖和葡萄糖耐量、尿白蛋白、肾小球中α_1Ⅳ型胶原和TGF-β1 mRNA的表达及肾脏病理改变。结果发现实验组小鼠血糖和葡萄糖耐量基本正常,但尿白蛋白/肌酐比值较对照组高出3.3倍,肾小球体积增大1.2倍,肾小球系膜基质增宽1.98倍,肾内Ⅳ型胶原沉积增多,肾小球中α_1Ⅳ型胶原mRNA和TGF-β1 mRNA表达明显增强。结论骨髓干细胞在STZ复制的糖尿病小鼠肾脏病变表型转移中具有重要作用。

Objective To investigate the role of bone marrow （BM） stem cells in the phenotype transfer of diabetic kidney disease. Methods C3H/He female mice with diabetes were induced by intraperitoneal injection of streptozotocin. Normal mice were given a lethall irradiation, then injected via intravenous with 5 ×10^6 BM stem cells from diabetic or normal control mice respectively. At 8 weeks after BM transplantation （BMT）, the intraperitoneal glucose tolerance test （IPGTT） was performed in the recipient mice. The urinary albumin/creatinine ratio was calculated for each group. Recipient mice were sacrificed at 8 weeks after BMT and the levels of a1 type Ⅳ collagen mRNA and TGF-β1 mRNA were measured using real-time RT-PCR. Total glomerular area and the mesangial area were obtained using the MetaMorph image analysis system. Type IV collagen was evaluated in the frozen tissues. Results There was no difference in IPGTT between two group, but the urinary albumin/creatinine ratio was 3.3-fold higher in diabetic mice BMT recipients than in the normal mice BMT recipients （P〈0.01）. Compared with the normal mice BMT recipients, diabetic mice BMT recipients had markedly increased values of the glomerular area, the ratio of mesangial area over glomerular area and the accumulation of type Ⅳ collagen in the glomerular mesangial space. The expression of a1 type IV collagen mRNA and TGF-Ⅲ mRNA in the kidney of the recipients of diabetic BMT were significantly increased （P〈0. 01）. Conclusions The BM stem cells play an important role in the nephrotic phenotype transfer of diabetic kidney disease.