中文摘要：

目的 探讨大鼠胰岛转染人血红素氧合酶-1（HO-1）基因在胰岛移植中的潜在应用价值。方法 采用携带人HO-1基因的腺病毒对新分离的SD大鼠胰岛细胞进行转染；对体外培养的胰岛细胞使用重组人肿瘤坏死因子a及放线菌酮诱导凋亡。使用流式细胞术检测凋亡率；每只链脲霉素诱导的糖尿病模型大鼠门静脉内置入约1200个胰岛当量的胰岛后，观察糖尿病大鼠血糖及体重变化；免疫组织化学法检测肝内移植胰岛细胞的胰岛素、HO-1蛋白表达及表达CD3抗原的淋巴细胞浸润情况。结果 转染人HO-1基因的胰岛细胞凋亡率明显低于对照组（P〈0．05）；单纯胰岛细胞移植后移植物存活时间为（5．33±4．18）d，转染人HO-1基因的胰岛细胞移植后移植物存活时间为（10．56±4.33）d，两组比较，P〈0．05；转染人HO-1基因的胰岛细胞培养48h即见人HO-1蛋白表达；肝内移植7d后移植物有人HO-1蛋白表达；移植胰岛周边及胰岛内淋巴细胞浸润程度较单纯胰岛移植组明显减轻。结论 大鼠胰岛转染人HO-1基因能够增加体外培养胰岛细胞的抗凋亡能力，并能延长体内移植胰岛的存活时间，减轻淋巴细胞对胰岛的浸润。

英文摘要：

Objective To investigate the effect of human heme oxygenase-1 （HO-1） gene on islets cultured in vitro engrafted in vivo, and explore the potential method of gene therapy in clinical islet transplantation. Methods Islets were isolated from Sprague-Dawley rats and transfected with adenovirus vector containing human HO-1 gene using MOI= 20. Flow cytometry was used to detect apoptotic cells after induction hy recombinant human tumor necrosis factor-α （rTNFα） and cyctohexmide （CHX） for 48 h. Using the portal vein as transplant site, about 1200 rat islet equivalents were transplanted into each streptozotocin induced diabetic Sprague-Dawley rat. Results Compared to simple transplant group apoptotic ratio was decreased significantly in HO-1 group after treatment with rTNF-α and CHX （P〈0. 05）. Maintenance of normoglycemia was prolonged in recipient rats carrying islets transfected with adenovirus vector containing HO-1 gene. Return of hyperglycemia in animals receiving untreated islets was （5. 33 ± 4. 18） clays while loss of function in the HO-1 group occurred at （10. 56 ± 4. 33） days. HO-1 protein was expressed in islet cells cultured for 48 h and transplanted for 7 clays in recipients＇ livers after HO-1 gene transduction. The degree of lymphocytic infiltration in HO-1 group was lower than that in control group. Conclusions Transfection of rat islets with Ad-HO-1 protects against rTNF-a and CHX mediated cytotoxicity. Islets transfected with adenovirus containing HO-1 can prolong graft survival in allogenic transplantation model. HO-1 gene can diminish the degree of lymphocytic infiltration in grafts.