监测Th1/Th2细胞因子变化对猪胰腺移植急性排斥反应早期诊断的意义

目的研究Th1／Th2型细胞因子IFN-γ／IL-4变化对胰腺移植手术后急性排斥反应早期诊断的意义。方法杂种长白猪24只，分为对照组、移植组和免疫抑制治疗组。移植组为同种异体胰十二指肠移植，免疫抑制治疗组在进行同种异体胰十二指肠移植手术同时应用环孢素A（CsA）＋霉酚酸酯（MMF）＋甲强龙三联治疗方案。术前1d和移植手术后1、3、5、7d采猪静脉血。检测血糖、胰岛素及胰高血糖素水平，流式细胞仪检测Th1／Th2型细胞因子IFN-γ和IL-4在CD4^＋细胞中的表达，并取移植胰腺组织进行病理学检查及进行评分。结果①术后1～7d移植组IFN-γ表达呈进行性上调，免疫抑制组轻度上调，在术后1、3、5、7d移植组与免疫抑制组IFN-γ的表达差异有统计学意义（P〈0．05）。②移植组IL-4的表达呈进行性下调，免疫抑制组IL-4表达进行性上调，在术后3、5、7d移植组和免疫抑制组IL-4的表达差异有统计学意义（P〈0．05）。③与对照组比较，移植组和免疫抑制组血糖、胰岛素及胰高血糖素水平的变化无统计学意义（P〉0．05）。④与移植组相比，免疫抑制组术后5d和7d胰腺排斥反应程度较轻（P〈0．05）。结论监测Th1（IFN-γ）和Th2（IL-4）型细胞因子变化可以早期发现胰腺移植后急性排斥反应。免疫抑制治疗可以下调Th1（IFN-γ）细胞因子表达，上调Th2（IL-4）型细胞因子的表达。

The Monitoring of Th1/Th2 Cytokine Expression and Its Significance to the Diagnosis of Acute Rejection after Pancreatic Transplantation

OBJECTIVE: To investigate the relationship between the change of Th1/Th2 cytokine expression in peripheral blood and the acute rejection or immune tolerance after pancreatic transplantation. METHODS: Twenty-four pigs of mixed inbreed were randomly divided into three groups, namely the control group, the transplantation group which was established by pancreatoduodenal allotranplantation, and the transplantation plus immunosuppression group which was brought into being in accordance to the immunosuppression regimen of CsA, MMF and metrisone after the pancreatoduodenal allotransplantation. The changes of the expression of Th1/Th2 cytokine in CD4+ T cells were detected by flow cytometry on the day before operation and on the first, 3rd, 5th ,and 7th day after operation; meanwhile, the levels of glucose, insulin and glucagons in systemic circulation were measured, and the tissues of pancreatic grafts were collected on the first, 3rd, 5th and 7th day after operation. RESULTS: IFN-gamma expression was up-regulated sharply from the first day to 7th day after transplantation in transplantation group and was up-regulated slightly in immunosuppression group. IFN-gamma expression showed significant difference between transplantation group and immunosuppression group on the first, 3rd, 5th and 7th day after transplantation (P < 0.05). IL-4 expression was down-regulated continuously in transplantation group, but up-regulated in immunosuppression group. IL-4 expression exhibited significant difference between transplantation group and immunosuppression group on the 3rd, 5th, and 7th day after transplantation (P < 0.05). In comparison with control, the levels of sugar, insulin and glucagons in blood displayed no significant difference between transplantation group and immunosuppression group (P > 0.05). In comparison with transplantation group, the immunosuppression group showed milder rejection on the 5th and 7th day after transplantation (P < 0.05). CONCLUSION: Change of expression of Th1 and Th2 cytokines may be an important parameter in determining whether acute rejection occurs after pancreatic transplantation.