Park Min-Jung, Na Hyun Sik, Joo Young-Shin, Cho Keun-Hyung, Kim Se-Young, Choi Jeong Won, Baek Jin-Ah, Choi Jong Young, You Young Kyoung, Cho Mi-La
The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Lab Anim Res. 2023 Mar 8;39(1):5. doi: 10.1186/s42826-023-00156-5.
Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model.
To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver.
Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.
原位肝移植是终末期肝病和肝细胞癌患者的唯一选择。移植后免疫抑制治疗对于预防移植物衰竭至关重要。我们在远交系大鼠肝移植模型中研究了他克莫司（FK506）的有效性及其诱导肝移植免疫耐受的机制。
为研究FK506对远交系大鼠肝移植模型的治疗效果，对移植大鼠每日皮下注射一次或两次FK506及进行术后治疗。对所有组进行组织病理学和免疫组织化学分析。通过流式细胞术分析脾脏中炎性细胞因子信号传导的调节情况。在大鼠原位肝移植模型中，FK506减轻了同种异体移植物排斥反应并提高了生存率。FK506治疗组的血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶水平降低。此外，FK506降低了肝脏中炎性细胞因子的表达以及致病性Th1和Th17细胞的活化。
综上所述，我们发现FK506通过抗炎作用和对致病性T细胞的抑制特性，改善了远交系肝移植模型中的强烈同种异体移植物排斥反应。
