根据CD4立体构型设计的新型免疫抑制物J2抑制小鼠胰岛移植急性排斥反应的初步观察  

Evaluation of a non-peptidic potential inhibitor of the interaction between CD4 and MHC class Ⅱ proteins in mouse pancreatic islets transplantation

作　　者：高杰[1] 朱继业[1] 刘沐芸 李涛[1] 张栋 沈丹华[1] 冷希圣[1] 

机构地区：[1]北京大学人民医院肝胆外科中心,100044 [2]深圳三九医药公司学术部 [3]Harvard Medical School, Beth Israel Deaconess Medical Center, Transplant Research Center

出　　处：《中华普通外科杂志》2007年第7期533-536,共4页Chinese Journal of General Surgery

基　　金：国家973计划资助项目（2003CB515508）.志谢 感谢军事医学科学院基础医学研究所沈倍奋院士与冯健男教授为本研究提供的帮助.

摘　　要：目的评价基于CD4立体构型设计的新型免疫抑制物J2对小鼠胰岛移植后急性排斥反应的影响。方法将900～1000个DBA/2（H-2^d）小鼠的胰岛移植在糖尿病模型C57BL/6（H-2^b）小鼠肾被膜下。移植前用台盼蓝和双硫腙染色检测胰岛细胞活性和纯度。将C57BL/6小鼠随机分为5组,每组10只,在胰岛移植后第1～10天腹腔内注射J2,每天一次。对照组注射生理盐水、CsA组注射环孢素A（10 mg/kg）;实验组J2A组（1mg/kg）、J2B组（4 mg/kg）、J2C组（8 mg/kg）。术后监测不同时间各组小鼠的血糖变化及移植胰岛的存活时间,并观察移植胰岛在术后第三天及发生急性排斥反应时的组织病理学及免疫组化表现。结果获得的胰岛细胞的活性＞95%,纯度＞85%。胰岛移植术前各组糖尿病小鼠的血糖平均高于20.0mmol/L,术后前四天各组小鼠的血糖下降明显,均低于11.1 mmol/L,且各组之间比较差异无统计学意义（P＞0.05）。移植第7天以后,对照组、J2A组小鼠的血糖较术后前四天明显升高（P＜0.05）。术后第八天开始,对照组、J2A组小鼠血糖升高平均高于11.1 mmol/L;CsA组、J2B组、J2C组的血糖仍低于11.1 mmol/L,三组之间无明显差异,但明显低于对照组和J2A组（P＜0.05）。病理学检查示移植后第三天各组移植的胰岛细胞轻度水肿,形态大致正常;移植后第八天对照组、J2A组的移植胰岛出现急性排斥反应病理改变,其他组病理未见排斥表现,小鼠胰岛素抗体免疫组化结果显示胰岛素阳性。CsA组（21.6±2.1 d）、J2B组（19.0±2.7d）、J2C组（18.7±2.3d）的移植胰岛存活时间比较差异无统计学意义,但分别较对照组（8.1±0.56d）、J2A组（8.3±0.48d）显著延长（P＜0.01）。结论一定剂量的J2具有和CsA相似的免疫抑制作用,可明显抑制小鼠胰岛移植后排斥反应的发生,显著延长移植物的存活时间。Objective To evaluate a small molecular weight non-peptidic potential inhibitor（J2） of the interaction between CD4 and MHC class Ⅱ proteins in mouse pancreatic islets transplantation. Methods In this study, 300 to 400 islets of DBA/2 （ H-2^d ） were to transplant into the renal subcapsular space of the diabetic model recipient C57BL/6（H-2^b）. The viability and purity of islets were determined by trypan blue and dithizone staining. Recipients were randomly divided into five groups （ten in each group）, J2 or immunosuppressant or control placebo were delivered by i.p. injection per day for 10 consecutive days post-transplantation. Group A was the control treated with NS. Group B was given CsA（ 10 mg/kg）. Groups C, D, E were given J2 at the dosage of 1 mg/kg, 4 mg/kg and 8 mg/kg respectively. Blood sugar and the survival time of grafts were monitored. The pathological and immunohistochemical changes of islet grafts were observed on day 3 and on the occurrence of rejection. Results The viability of islets was more than 95% with purity over 85%. Blood sugar level of all mice model were over 20. 0 mmol/L, and declined（ 〈 11.1 mmol/L） on day 1-4 after islets transplantation. After day 7, blood sugar of the control and group C were significantly higher than that of day 1 - 4 （ P 〈 0.05 ）, and higher than 11.1 mmol/L from day 8. Blood sugar of group B, D and E （ still 〈 11.1 mmol/L） was not statistically different, but lower than that of the control and group C（P〈0. 05）. There was no rejection in all groups on day 3 but grafts suffered from acute rejection in group A and C on day 8 post-operation, other groups were normal by pathology and immunohistochemical staining was positive for mouse insulin-Ab. The survival time of grafts of group B （21.6±2. 1 d） ,D（ 19.0±2. 7 d） and E（ 18. 7±2. 3 d） were significantly longer than the control （8. 1 ± 0.56d） and group C （ 8. 3 ± 0. 48 d）（P〈0.01）. Conclusion J2 effects immunosuppressive action as CsA, it can d

关 键 词：胰岛移植 小鼠 免疫抑制剂 环孢素A CD4 

分 类 号：R686[医药卫生—骨科学]