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作 者:刘骏[1] 芮晓晖[1] 王乾伟[1] 张群华[1] 陈宗祜[1]
机构地区:[1]复旦大学附属华山医院普外科,上海200040
出 处:《中华医学杂志》2009年第48期3437-3440,共4页National Medical Journal of China
摘 要:目的探讨聚乙二醇(PEG)包埋小鼠胰岛细胞对同种小鼠胰岛移植物存活的影响,以及其与抗排斥药雷帕霉素共同应用对胰岛移植后抗排斥治疗的影响。方法选取C57BIJ6雄性小鼠皮下预血管化糖尿病模型,行BALB/c小鼠胰岛移植。随机分为6组:A组:正常胰岛移植组。B组:PEG包埋胰岛移植组。C组:正常胰岛移植+雷帕霉素1.5mg·kg^-1·d^-1治疗组。D组:PEG包埋胰岛移植+雷帕霉素1.5mg·kg^-1·d^-1治疗组。E组:正常胰岛移植+雷帕霉素3mg·kg^-1·d^-1治疗组。F组:PEG包埋胰岛移植+雷帕霉素3mg·kg^-1·d^-1治疗组。观察小鼠血糖变化,病理检测移植物存活情况。结果B组胰岛存活时间(25.5±5.9)d较A组(14.7±2.6)d明显延长(P〈0.01),C组胰岛存活时间(35.0±3.1)d,D、E、F组胰岛于移植后6周均存活。HE染色下B组较A组炎症反应轻,胰岛结构完整。免疫组化染色显示B组有散在染色增强细胞团而A组未见。结论PEG包埋胰岛细胞可显著延长移植物的存活时间,并能减少免疫抑制剂雷帕霉素的用量。Objective To investigate the impact of polyethylene glycols(PEG) upon islet survival in homogeneous murine islet transplantation and understand the impact of PEGylation in combination with rapamycin upon anti-rejection therapy in homogeneous mice islet transplantation. Methods The subcutaneously pre-vascularized STZ-induced diabetic mice treated with transplanted islets of BALB/c mice were randomly divided into 6 groups: Group A with normal mice islets; Group B with PEG-packed islets; Group C with normal mice islets and 1.5 mg·kg^-1·d^-1 rapamycin ; Group D with PEG-packed islets and 1.5 mg·kg^-1·d^-1 rapamycin; Group E with normal mice islets and 3 mg·kg^-1·d^-1 rapamycin; Group F with PEG-packed islets and 3 mg·kg^-1·d^-1 rapamycin. The post-transplantation blood glucose was monitored. Transplanted islets were analyzed by H&E and insulin immunostain. Results The survival time in group B was significantly prolonged as compared with group A (P 〈 0. 01 ). The survival time in group C were (35.0 ± 3.1 ) d and groups D, E, F had survival of up to 6 weeks. Transplantation sites of group A were observed with a more abundant infiltration of immune cells than group B. And the unmodified islets in group A were completely destroyed after transplantation. Insulin-positive islet cells were not detected at the entire transplantation site in group A while the presence was found at the transplantation site in group B. Conclusion PEG-packed islets can significantly improve the survival time of transplanted islets. When combined with rapamycin, it can reduce the dose of rapamycin.
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