磁标记内皮祖细胞移植对糖尿病大鼠肾功能改善的作用:MRI成像验证

Effect of magnetic labeled endothelial progenitor cell transplantation on renal function of diabetic rats: a MRI imaging verification

背景:近几年的诸多研究发现,内皮祖细胞在损伤性疾病等方面有重要作用。目的:探讨磁标记内皮祖细胞移植对糖尿病大鼠肾功能的改善作用及MRI成像。方法:将60只Wistar大鼠随机分为3组,正常对照组不作任何处理;模型组、实验组腹腔注射40 mg/kg链脲佐菌素,建立1型糖尿病模型,造模后4周,实验组尾静脉注射磁标记内皮祖细胞悬液0.15 m L(细胞浓度1×109 L-1)。细胞移植8周后,检测3组大鼠空腹血糖、血清胰岛素、血肌酐和尿素氮及24 h尿蛋白水平;采用MRI对移植细胞进行活体示踪,并与肾脏组织切片进行对照;测量大鼠体质量及肾质量变化,计算肾质量指数。结果与结论:(1)与正常对照组比较,模型组空腹血糖、血肌酐和尿素氮、24 h尿蛋白及肾质量指数升高(P<0.05),胰岛素水平降低(P<0.05);(2)与模型组比较,实验组空腹血糖、血肌酐、尿素氮、24 h尿蛋白及肾质量指数降低(P<0.05),胰岛素水平升高(P<0.05);(3)实验组可见稍长T1短T2信号,病灶边缘部位明显,梯度回波FLASH序列较T2加权RARE序列明显,其余组均未见明显低信号改变;实验组可见磁标记的阳性细胞且与组织切片结果相吻合,模型组和正常对照组未见磁标记的阳性细胞;(4)结果表明,磁标记内皮祖细胞移植可在一定程度上改善糖尿病大鼠的肾功能紊乱。

BACKGROUND： Endothelial progenitor cells have been shown to play an important role in the pathogenesis of traumatic diseases in recent years.OBJECTIVE： To explore the effect of magnetic labeled endothelial progenitor cell transplantation on renal function of diabetic rats through a MRI imaging study.METHODS： Sixty Wistar rats were randomly divided into normal（no treatment）, control and experimental groups. Intraperitoneal injection of 40 mg/kg streptozotocin was performed to make a rat model of type 1 diabetes in the control and experimental groups. Four weeks after modeling, rats in the experimental group were given intravenous injection of magnetic labeled endothelial progenitor cells（0.15 m L, 1×109/L）. Fasting blood glucose, serum insulin, serum creatinine, urea nitrogen and 24-hour urinary protein levels in rats were measured at 8 weeks after cell transplantation. MRI was used to trace transplanted cells in vivo in comparison with renal biopsy findings, and rat body mass and kidney weight were measured to calculate kidney weight index. RESULTS AND CONCLUSION： After modeling, fasting blood glucose, serum creatinine, urea nitrogen and 24-hour urinary protein levels as well as kidney weight index were increased significantly（P〈0.05）, while the insulin level decreased（P〈0.05）. Compared with the model group, the endothelial progenitor cell transplantation reversed these indices（P〈0.05）. Additionally, in the experimental group, there was slightly longer T1 and shorter T2 signals as well as marked lesion edge, and the FLASH sequence became more remarkable compared with the T2-weighted RARE sequence. The other groups showed no significant low signal changes. Magnetic-labeled positive cells in the experimental group showed by the MRI were consistent with the tissue biopsy results, while no positive cells were found in the model and normal groups. To conclude, the magnetic labeled endothelial progenitor cell transplantation can improve renal dysfunction in diabetic rats to a certain extent.