Li Haibo, Fang Yuan, Li Xu, Chen Jingting, Xiong Yao, Shi Yongzhou, Li Shengli, Ye Lincai, Wang Shoubao, Zhou Jianda
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
J Inflamm Res. 2022 Oct 28;15:6021-6030. doi: 10.2147/JIR.S383628. eCollection 2022.
The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival.
Firstly, we used Brown Norway rats and Lewis rats to construct animal model of VCA. Regularly record the appearance changes of all subjects. Specimens were collected for histological examination, microRNAs (miRNAs) sequencing and RT-qPCR verification when acute immune rejection occurred. Then, bioinformatics analysis was employed to predict miRNA related molecules and pathway information. Finally, differentially expressed miRNAs were tested and verified.
MiRNAs are small non coding RNA transcripts that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs are involved in immune regulation and several miRNAs have been identified that are potential diagnostic and prognostic biomarkers of acute rejection. In this study, we found that the expression levels of rno-miR-21-5p, rno-miR-340-5p, rno-miR-1-3p and rno-miR-195-5p are significantly associated with acute rejection following VCA.
This miRNA signature can potentially an auxiliary diagnostic indicator of rejection, which can help clinicians adjust the immunosuppressive program in time during acute rejection.
显微外科的发展极大地推动了血管化复合组织异体移植（VCA）。然而，与器官移植一样，VCA也受到急性排斥反应的限制，并且存在关于移植移植物长期存活和功能的担忧。因此，有必要阐明VCA引起的急性排斥反应的分子机制，以提高患者生存率。
首先，我们使用棕色挪威大鼠和刘易斯大鼠构建VCA动物模型。定期记录所有受试对象的外观变化。在发生急性免疫排斥反应时收集标本进行组织学检查、微小RNA（miRNA）测序和RT-qPCR验证。然后，采用生物信息学分析来预测miRNA相关分子和通路信息。最后，对差异表达的miRNA进行检测和验证。
miRNA是在转录后水平调节基因表达的小非编码RNA转录本。研究表明，miRNA参与免疫调节，并且已经鉴定出几种miRNA是急性排斥反应的潜在诊断和预后生物标志物。在本研究中，我们发现rno-miR-21-5p、rno-miR-340-5p、rno-miR-1-3p和rno-miR-195-5p的表达水平与VCA后的急性排斥反应显著相关。
这种miRNA特征可能成为排斥反应的辅助诊断指标，有助于临床医生在急性排斥反应期间及时调整免疫抑制方案。
