磁共振成像监测大鼠肝脏内经超顺磁铁氧化物标记的胰岛移植物

目的 探讨磁共振成像(MRI)监测胰岛移植物的可行性.方法 在体外利用超顺磁铁氧化物(SPIO)标记大鼠胰岛,然后移植至用链佐星诱导的糖尿病大鼠肝脏内,同系移植标记组供、受者均为Wistar大鼠,同种移植标记组供者为Lewis大鼠,受者为Wistar大鼠.并设同系移植对照组(供、受者均为Wistar大鼠)和同种移植对照组(供者为Lewis大鼠,受者为Wistar大鼠),胰岛移植物未经SPIO标记.术后定期利用MRI监测肝内胰岛移植物,监测受者的血糖,并抽取动物,对其肝脏进行病理检查.结果 只有SPIO标记的胰岛移植物能被MRI检测到.经MRI检测,同系移植标记组术后第1、2、3周胰岛移植物的相对数量分别为(89.6±2.2)%、(87.5±14.4)%和(74.5±19.5)%,同种移植标记组术后第1、2、3周的相对数量分别为(43.2±17.2)%,(36.5±13.0)%和(26.5±17.4)%,组间相同时间点两两比较,差异有统计学意义(P<0.05).同系移植标记组血糖始终维持在正常水平,肝脏中能检测到胰岛素免疫组化和普鲁士蓝染色双阳性细胞;而同种移植标记组移植1周后的血糖水平超过16.8 mmol/L,肝脏中无法找到形态完整的胰岛.结论 MRI监测结果与血糖监测和病理检查结果一致,但它可直观、无创、连续地监测胰岛移植物在体内分布和存活情况.

Monitoring of SPIO labeled islet grafts in liver of diabetic rats by MRI imaging

Objective To investigate the possibility of monitoring superparamagnetic iron oxide (SPIO) labeled islet grafts in vivo by magnetic resonance imaging (MRI). Methods Islet grafts were labeled with SPIO in vitro and transplanted into the liver of streptomycin-induced diabetic rats. There were 4 groups, including 2 syngeneic groups (Wistar to Wistar transplantation, one group receiving SPIO labeled islets,and the other group unlabeled islets as control) and 2 allogeneic groups (Lewis to Wistar transplantation, one group receiving SPIO labeled islets, and the other group unlabeled islets as control). Poly-L-Lysine (PLL) was used to increase the labeling efficiency of SPIO. After transplantation, MRI was performed regularly, fed glucose level was monitored, and animals were sampled for pathological examination. Results Only SPIO labeled islets could be detected by MRI. The relative number of islets detected by MRI in syngeneic group receiving labeled islets at week 1,2 and 3 following transplantation was (89.6±2.2)%, (87.5±14.4)% and (74.5±19.5)% respectively, and the relative number in allogeneic groups receiving labeled islets at these time points were (43.2±17.2)%, (36.5±13.0)% and (26.5±17.4)% respectively. Statistical significance was observed as the result of a paired student's t test (P<0.05). In the syngeneic groups, hyperglycemia was under well control, and co-localization of insulin activity and Prussian blue staining was observed in the liver sections of the animals receiving labeled islets. Meanwhile, in the allogeneic groups, loss function of islet grafts was determined by fed glucose level > 16.8 mmol/L at first week following transplantation,and no intact islets could be found in liver sections since that time. Conclusion Results of MRI correlate to fed glucose level monitoring and pathological examination. Application of this elegant imaging technique provides a direct, noninvasive and continuous way to monitor the distribution and survival of islet grafts in vivo.