BACKGROUND The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS. METHODS Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels. RESULTS The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate. CONCLUSIONS This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (TD = - 0.494TC-0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.

中文翻译：

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接近治疗大鼠活体肝移植免疫排斥反应。

背景技术活体肝移植（LDLT）后小型综合征（SFSS）的抗免疫排斥治疗在维持移植物存活方面发挥着核心作用。肝细胞数量和移植物功能随着移植物再灌注后的增殖和凋亡而发生实时变化。缺乏准确有效的治疗方案或指标来指导SFS肝移植中免疫抑制药物的使用，使得SFS肝移植后的免疫治疗成为亟待解决的问题。在此，我们建立了大鼠小尺寸（SFS）和正常尺寸肝移植模型，以探索指导免疫治疗的有效指标，寻找克服SFSS的有效途径。方法 Lewis 大鼠（供体）和 BN 大鼠（​​受体）用于模拟同种异体肝移植并用他克莫司治疗。通过苏木精和伊红和免疫组织化学分析局部移植物免疫反应。流式细胞仪用于评估受体的整体免疫状态。通过在mRNA水平和蛋白质水平检测CYP3A2的表达，探索免疫抑制药物的药代动力学机制。结果肝移植后4天，SFS移植物的局部免疫反应和受者的全身免疫反应较正常大小的移植物和受者明显增加。采用回归方程调节他克莫司剂量，既能有效控制他克莫司血药浓度，又能减轻肝损伤，提高存活率。结论 本研究表明AST水平和他克莫司血清浓度是指导免疫治疗的有效指标。基于AST和他克莫司血药浓度的回归方程（TD=-0.494TC-0.0035AST+260.487）可作为SFS肝移植术后免疫治疗调整的参考，适用于临床。