免疫耐受模型的建立与胰岛移植的研究

Establishm ent of the im m une tolerance anim al m odel and islettransplantation

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。结果发现：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。

The purpose of this study is to establish the donor specific tolerance new anim alm odeland apply this m odel to investigate the relationship of im m une tolerance w ith islettransplantation, and the relationship of physiologic function in graft site w ith the survival andfunction of islet graft. Results:① By intrathym ic or intraportal inoculation w ith donor cellularantigen and treatm ent w ith antilym phocyte serum and cyclophosphoram inde ( A L S+ C P), thetolerant rats have been established, The survivaltim e ofskin and islet allograft w ere prolonged inthis tolerant m odel. ② In the tolerant m odel: the survival of allo or xeno islet grafts w eresignificantly prolonged w ith increased insulin contents and norm alized glucose levels. Thesurvival of intraportal or intrasplenic islet graft w ere confirm ed by functional and histologicalfinding, It suggests that the spleen is as suitable a site for islet graft as the liver. ③ Theprolifieration of lym phocyte in m ixed lym phocyte pancreatic acinar cell coculture( M L A C) w asinhibited by hepatocytes. It suggested that hepatocyte could have a potential to inhibit theim m une reactions to islet grafts. ④ In hepatocyte - islet coculture, the insulin content of isletrelease w ere significantly reduced w hen hepatocyte w as added. It could have som e relationshipsw ith hepatocytes or its factors. ⑤ In portal vein of rat, the distributed αadrenoceptor subtypesare α1 and α1 A. These receptors w ere show n to m ediate the regulation of portalcirculation. In ratof spleen, α1 and α2 subtypes of αadrenoceptor w ere found. These receptors w ere proved tom ediate the contraction of spleen.