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免疫耐受模型的建立与胰岛移植的研究(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
1999年第3期
页码:
175-178
栏目:
博士之窗
出版日期:
1999-05-01

文章信息/Info

Title:
Establishment of the immune tolerance animal model and islet transplantation
作者:
保庭毅 指导教师: 臧益民 辅导教师: 牛国保　吴金生
第四军医大学生理学教研室　西安 710032
Author(s):
Bao Tingyi (Postgraduate); Zang Yimin(Director)
Department of Physiology, Fourth Military Medical University, Xi′an 710032
关键词:
免疫　耐力　胰岛　移植　脾脏　门静脉　肝细胞
Keywords:
immunity　tolerance　islet　transplantation　spleen　portal`vein ;  hepatocyte.
分类号:
-
DOI:
-
文献标识码:
-
摘要:
本研究试图建立供体特异性的免疫耐受动物模型,并探索胰岛移植与免疫耐受的关系, 探讨移植区生理与胰岛存活和功能的关系。果发现: ①从免疫应答和皮肤、胰岛移植物存活等结果,证实了经胸腺或门脉植入细胞(脾细胞和骨髓细胞或肝细胞)抗原,是建立免疫耐受的有效途径; 植入细胞抗原和联合应用免疫抑制剂(抗大鼠淋巴细胞血清加环磷酰胺) 可诱导免疫耐受; ②在建立免疫耐受模型基础上, 发现脾内或肝(门脉内) 胰岛移植物有功能存活期明显延长,且渡过了急性排斥期;胰岛在脾内或肝内生长良好;均能逆转受者的高血糖状态,提示脾内与门脉内一样是胰岛移植的适宜场所。③肝细胞能抑制胰腺细胞介导的受体淋巴细胞增殖, 提示肝细胞具有抑制胰腺细胞介导的急性排斥反应作用。④在肝细胞-胰岛细胞共培养条件下,胰岛分泌胰岛素大幅度减少,其机制可能是肝细胞或来源于肝脏的某种因子具有抑制胰岛分泌胰岛素作用。⑤脾脏分布α1,α2受体,且α1受体亚型介导的收缩效应并不依赖细胞外Ca2+的存在。门静脉分布以α1受体为主,且α1受体亚型的缩血管效应依赖于细胞外Ca2+ 的存在。
Abstract:
The purpose of this study is to establish the donor specific tolerance new animal model and apply this model to investigate the relationship of immune tolerance with islet transplantation,and the relationship of physiologic function in graft site with the survival and function of islet graft. Results:①By intrathymic or intraportal inoculation with donor cellular antigen and treatment with antilymphocyte serum and cyclophosphoraminde(ALS+CP),the tolerant rats have been established, The survival time of skin and islet allograft were prolonged in this tolerant model. ② In the tolerant model: the survival of allo-or xeno-islet grafts were significantly prolonged with increased insulin contents and normalized glucose levels. The survival of intraportal or intrasplenic islet graft were confirmed by functional and histological finding, It suggests that the spleen is as suitable a site for islet graft as the liver.③ The prolifieration of lymphocyte in mixed lymphocyte pancreatic acinar cell coculture(MLAC)was inhibited by hepatocytes. It suggested that hepatocyte could have a potential to inhibit the immune reactions to islet grafts.④ In hepatocyte-islet coculture,the insulin content of islet release were significantly reduced when hepatocyte was added. It could have some relationships with hepatocytes or its factors.⑤In portal vein of rat, the distributed αadrenoceptor subtypes are α1 and α1α.These receptors were shown to mediate the regulation of portal circulation. In rat of spleen, α1 and α2subtypes of α adrenoceptor were found.These receptors were proved to mediate the contraction of spleen.

参考文献/References

［1］Exner BG,Fowler K,Ildsted ST.Tolerance induction for islet transplantation.Ann Transplant, 1997;2(3):77.

［2］Manilay JO,Pearson DA,Sergio JJ,et al.Intrathymic deletion of alloreactive T cells in mixed bone marrow chimeras prepared with a nonmyeloablative conditioning regimen.Transplantation,1998;66 (1):96.

［3］Remazzi G.Cellular bass of long-term organ transplant acceptance pivotal role of intrathymic clonal deletion and thymic dependence of bone marrow microchimerism associated tolerance. Am J Kid ney Dis,1998;31(2):197.

［4］Sugiura K,Kato K, Hashimoto F, et al.Induction of donor sppecific T cell anergy by portal venous injection of allogeneic cells. Immunobiology,1997;197(5):460.

［5］ Yu S,Nakafsa Y,Flye MW.In vitro analysis of gadolinium chloride abrogation of the systemic tolerance induced by portal venous administration of ultraviolet B*irradiated donor cells.Trasplantation,1997;64(12):1684.

［6］Perez RV,Swanson C,Morgan M,et al.Portal venous transfusion up-regulatals kupffer cell cycloorygenase activityly mechanism of immunosuppression in organtransplantation.Trasplantation, 1997;64(1):135.

［7］Miyauchi T,Ishikawa M,Tashiro S,et al.Effect of donor-specific splenocytes via portal vein and FK506 in rat small bowel transplantation. Transplantation, 1998;65(1):27.

［8］ Domhrowcki F,Klingmuller D,Pfeifer U.Insulinomas derived from hyperplastic intrahepatic islet transplants. Am J Pathol,1998;152(4):1025.

［9］Evert M,Dombrowski F,Schirmacher P,et al.Nonparenchymal cells in chronically hyperinsulinemic liver acini of diabetic rats, with special regard to hepatic stellate cells.J Hepatol,1998;28(4):709 .

［10］Bottino R,Fernandez LA,Pricordi C,et al.Transplanation of allogeneic islets of Langerhans in the rat liver:effects of macrophage depletion on graft survival and microenvironment activation. Diabetes,1998;47(3):316.

［11］保庭毅,吴金生, 何泽生,等.大鼠门静脉α肾上腺素受体亚型的分布及功能.心功能杂,1999;11(2):88.

［12］保庭毅,何泽生,吴金生,等.大鼠脾脏收缩功能与α肾上腺素受体亚型的调节.心功能杂志,1999;11(2) : 95.

备注/Memo

备注/Memo:
(收稿1999-06-16　修回1999-06-24)
更新日期/Last Update: 1999-05-01