BOLD MRI对糖尿病大鼠肾脏早期损伤的动态评估研究

Evaluation of early renal injury development in diabetic rats using BOLD MRI

目的 :磁共振血氧水平依赖成像(BOLD MRI)对糖尿病大鼠模型及正常对照组进行肾内氧和代谢动态评估,确定BOLD MRI成像对糖尿病肾脏早期损伤评价的意义。方法 :将造模成功的62只糖尿病大鼠作为实验组(DN组,n=62),正常10只大鼠作为对照组(NC组,n=10)。NC组作为BOLD MRI扫描基线,DN组在造模成功后3,7,14,21,28,35,42,49,56,63和70天成像。获得肾脏皮髓质R2*值(CR2*,MR2*)及髓皮质R2*值比值(MCR)。同时检测DN组大鼠微量蛋白尿(UAE)以及大鼠肾脏病理标本评估肾小球硬化指数(GSI),系膜容积(Vvmes),肾小球毛细血管面积(Svcap)的检测。结果:DN组CR2*和MR2*值逐渐上升,与正常对照组比较有显著差异。在35天达到最高值(MR2*=(43.79±1.46)s^(-1),CR2*=(33.95±0.34)s^(-1));之后有所下降至第70天为MR2*=(41.61±0.95)s^(-1),CR2*=(33.17±0.69)s^(-1),但仍高于NC组(P<0.01)。MCR亦呈先升后降的动态过程,42天达到高峰1.32,70天时为1.25。DN组大鼠的生化指标以及病理学检查数据均有增高,与对照组比较呈显著差异。其中大鼠成模第7天DN组与NC组的UAE出现显著差异(P<0.01)。结论:BOLD MRI可以对糖尿病引起的肾脏损伤的动态过程进行氧代谢方面的无创性评估,且比微量白蛋白能更早的反应出肾脏病理生理变化;本实验获得MCR的动态改变可能提示肾脏损伤从功能性高渗代偿进入器质性病变如系膜基质增生、肾小球硬化等病变。

Objective： To observe changes in renal oxygenation levels using BOLD MRI, and to evaluate the usefulness of BOLD MRI in development of early diabetic renal injury. Methods： A total of 62 diabetic rats with successful modeling were used as the experimental group （DN group, n=62）, and 10 normal rats served as the normal control group （NC group, n=10）. The NC group was used as the baseline for the BOLD MRI scan, and the rats in the DN group underwent MR imaging at 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, and 70 days after modeling. Renal cortical and medullary R2＊ （CR2＊, MR2＊） values were measured and R2＊ ratio between medulla and eortex（MCR） was calculated. The urine albumin concentration and histopathologteal examination （GSI, Vvmes, Sveap） were evaluated at different time points. Results： CR2＊ and MR2＊ values of DN group were significantly higher than those of NC group. Those R2＊ values raised gradually and reached the peak at 35 days（CR2＊= （33.95±0.34） s^-1, MR2＊=（43.79±1.46）s^-1, then dropped gradually at 70 days（CR2＊=（33.17±0.69）s^-1, MR2＊=（41.61±0.95）s^-1）, MCR in DN group gradually inereased to the peak of 1.32 at 42 days and then decreased to 1.25 at 70 days. UAE of DN group increased gradually, it was significantly higher than that of NC group at 7 days（P〈0.01）. The GSI and Vvmes and Sveap were higher in DN group compared to NC group（P〈0.01）. Conclusions： BOLD MRI can noninvasively evaluate the renal hypoxia in diabetes and detect diabetic renal injury earlier than UAE. The dynamic changes of MCR in our study may suggest that renal injury may be from functional hypertonic compensation into organic lesions such as mesangial proliferation and glomeruloselerosis.