恒河猴肝移植模型移植后急性排斥反应时肿瘤坏死因子α的变化

背景：肿瘤坏死因子α是一种炎性细胞因子，参与移植免疫反应并增加移植物抗原表达，并在其中发挥着重要作用。目的：分析恒河猴肝移植后肝组织中肿瘤坏死因子α的变化与急性排斥反应的关系。方法：采用改良血管袖套＋胆道支撑管＋动脉吻合法建立稳定的恒河猴肝移植模型，将其随机分为实验组（围手术期不给予免疫抑制治疗）和对照组（围手术期给予免疫抑制治疗）。分别在移植后6，12，24和72h4个时间点分别收集血清及肝脏组织，检测肝功指标变化，通过苏木精-伊红染色Banff评分评定其移植排斥反应情况，并最终应用免疫组织化学技术、蛋白印迹分析分别检测肿瘤坏死因子α的表达水平。结果与结论：实验组和对照组肿瘤坏死因子α的表达在移植后6h即开始增高，至12h时达到高峰，24-72h降低，并且实验组变化最明显。移植后6，12，24和72h4个时间点组实验组肿瘤坏死因子α蛋白表达明显高于对照组（P〈0.05），此变化早于肝组织病理学及肝功能的改变。提示肝移植后肝组织肿瘤坏死因子α的表达水平变化，对肝移植后急性排斥反应的早期诊断具有重要意义。

Variation of tumor necrosis factor-alpha during acute rejection after liver transplantation in a rhesus monkey

BACKGROUND：Tumor necrosis factor-αis an inflammatory cytokine involved in the immune response and increasing graft antigen expression. OBJECTIVE：To investigate the relationship between tumor necrosis factor-αin the liver tissue and acute rejection after liver transplantation in a rhesus monkey. METHODS：Liver transplant models in rhesus monkey were constructed by the improved vascular dual cuff, supporting tube of biliary tract and artery anastomosis method. The successful models were randomly divided into experimental group （no immunosuppressant treatment in perioperative period） and control group （treated by immunosuppressant in perioperative period）. Then the blood samples and liver tissue were col ected at 6, 12, 24, and 72 hours after surgery. Al ograft rejections of liver transplantation were monitored by liver function tests, hematoxylin-eosin staining and Banff score. Final y, the expression level of tumor necrosis factor-αwas detected by western blot analysis and immunohistochemistry technique. RESULTS AND CONCLUSION：The expression of tumor necrosis factor-αin the experimental group and control group began to increase at 6 hours, reached the peak at 12 hours, and then decreased at 24-72 hours. The changes of expression level were the most obvious in the experimental group. At 6, 12, 24 and 72 hours, the expression of tumor necrosis factor-αin the experimental group was significantly higher than that in the control group （P〈0.05）. This change appeared earlier than pathological changes in the liver and liver function. Variations in the expression of tumor necrosis factor-αafter liver transplantation have important implications for early diagnosis of acute rejection after liver transplantation.