胃黏膜下胰岛移植减轻移植物损伤的机制

Mechanisms of the alleviation of islet graft injury in the gastric submucosa

目的 研究胃黏膜下层胰岛移植减轻移植物早期损伤的机理.方法 实验分为胃黏膜下胰岛移植组（n=8）和肝门静脉胰岛移植组（n=8）.将1200IEQ SD大鼠胰岛细胞分别移植入链脲佐霉素（STZ）诱导的糖尿病SD大鼠胃黏膜下层和肝门静脉内.术后第14天行葡萄糖耐量试验和病理组织学检测,分别检测术后30 min两组C肽和术后12 h两组IL-1β和TNF-α水平.结果 胃黏膜下组平均存活时间为（25.9±4.1）d,而肝门静脉组平均存活时间为（16.0±0.8）d,两组相比差异有统计学意义（P＜0.01）.术后第14天,葡萄糖耐量试验以及胰岛素和Tunnel-DAPI免疫荧光染色证实,胃黏膜下层胰岛移植物存活及功能良好.与胃黏膜下组相比,肝门静脉组术后30 min C肽明显升高[（1.46±0.28） ng/ml比（3.84±0.22） ng/ml,P＜0.01].此外,与胃黏膜下组相比,术后12 h门静脉组IL-β[（29±1.41） pg/ml比（262.26±53.37） pg/ml]和TNF-α[（23±1.41） pg/ml比（138.51±39.50） pg/ml]亦明显升高（P＜0.01）.结论 胃黏膜下层胰岛移植能通过避免或减轻血液介导的即刻炎症反应（IBMIR）和胰岛移植物损伤,延长胰岛移植物存活时间.

Objective To investigate the mechanisms of the alleviation of islet graft earlier injury in the gastric submucosa.Methods The recipients were divided into gastric submucosa group （n =8） and hepatic portal vein group （n =8）.1200IEQ SD rat islets were transplanted into diabetic SD rats induced by the administration of streptozocin （STZ）.Glucose tolerance test and pathological examination were performed 14 days post transplantation.30 min after the transplantation,the C-peptide of the two groups were detected.12 h after the transplantation,IL-1β and TNF-α of the two groups were examined.Results The mean survival time （MST） of grafts in gastric submucosa group was （25.9 ± 4.1） d and （16.0 ± 0.8） d （P ＜0.01） in portal vein group.The results of glucose tolerance test and immunofluorescent staining demonstrated that grafts in gastric submucosa group survived well and got excellent function 14 days post transplantation.Compared with the gastric submucosa group,after 30 min of the transplantation,C-peptide in portal vein group was significantly higher [（1.46 ± 0.28） ng/ml.vs.（3.84 ± 0.22） ng/ml,P ＜ 0.01].Additionally,the level of IL-1β [（29 ± 1.41） pg/ml.vs.（262.26 ± 53.37） pg/ml,P ＜ 0.01] and TNF-α [（23 ± 1.41） pg/ml.vs.（138.51 ± 39.5） pg/ml,P ＜ 0.01] in portal vein group,were also significantly higher than the gastric submucosa group,after 12 h of the transplantation.Conclusion Islet transplantation in gastric submucosa prolongs islet grafts survival by avoiding or alleviating IBMIR and the injuries induced by early inflammatory mediators.