机构：[1]Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China.[2]Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
To establish an animal model of pre-sensitization following liver transplantation either with or without immunosuppressors. To study whether accelerated liver rejection or acute antibody-mediated rejection (AMR) occurred and study the characteristics and potential mechanism in the animal model.Lewis (LEW) rats were subjected to liver [liver graft of Brown Norway (BN) rat] transplantation 2 weeks after lymphocyte injection (lymphocytes of BN rat; pre-sensitization). At 2 weeks after transplantation, serum samples of recipients were collected for antibody analysis to identify donor-specific alloantibody (DSA) level. The recipients were treated with or without a low dose of immunosuppressor (2 mg/kg). The liver grafts of each group were analyzed by hematoxylin and eosin (HE) stain, Masson stain, CK19, C4d, and CD20 immunohistochemical (IHC) stain, CD3, CD68, and CD86 immunofluorescence and transmission electron microscope (TEM) to study the characteristics of liver rejection. Moreover, cytotoxin-associated genes, M1 macrophages conversion-related proteins, and interleukin-6 (IL-6) signaling pathway proteins were detected by western blotting.High level of DSA and accelerated liver rejection occurred in the pre-sensitized rat models following liver transplant. Accelerated liver graft rejection occurred in the pre-sensitized, post liver transplant rats regardless of whether a low dose immunosuppressor had been applied. Severe injury of the interlobular bile ducts and accelerated fibrosis could be observed. Moreover, evidence of endothelial injury, such as capillary inflammation, was found in the pre-sensitized, post-transplant rats. In addition, C4d deposition and M1 macrophages recruitment were also found in this sensitized followed transplant model, indicating that complement activation might occur in this model. The levels of IL-6, JAK1, STAT3, SHP2, and ERK1-2 were increased in the pre-sensitized, post-transplant rats.Pre-sensitized post liver transplant rats might be potential AMR models for further study.2022 Annals of Translational Medicine. All rights reserved.
基金：
This study was supported by grants from the Clinical Medical Center for Organ Transplantation of Yunnan Province (No. ZX2019-07-01), Health Science and Technology Planning Project of Yunnan Province (No. 2018NS0161), and The Science and Technology Planning Project of the Science and Technology Agency of Yunnan Province (No. 202201AY070001-198).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|4 区医学
小类|4 区医学：研究与实验4 区肿瘤学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China.[2]Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.[*1]Department of Hepato-Biliary-Pancreatic surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People’s Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province,1228 Beijing Road, Kunming, Yunnan, China.[*2]Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, 1168 Chunrong West Road, Kunming 650500, Yunnan, China
推荐引用方式(GB/T 7714)：
Mang Yuanyi,Zhang Shengning,Zhao Jiaojiao,et al.Characteristics of pre-sensitization-related acute antibody-mediated rejection in a rat model of orthotopic liver transplantation[J].Annals of translational medicine.2022,10(19):1066.doi:10.21037/atm-22-4311.
APA：
Mang Yuanyi,Zhang Shengning,Zhao Jiaojiao,Ran Jianghua,Zhao Yingpeng...&Bao Fukai.(2022).Characteristics of pre-sensitization-related acute antibody-mediated rejection in a rat model of orthotopic liver transplantation.Annals of translational medicine,10,(19)
MLA：
Mang Yuanyi,et al."Characteristics of pre-sensitization-related acute antibody-mediated rejection in a rat model of orthotopic liver transplantation".Annals of translational medicine 10..19(2022):1066
