miR-27a-5p 通过 PI3K/Akt 通路诱导枯否细胞 M2 极化，抑制大鼠肝移植急性排斥反应。
miR-27a-5p inhibits acute rejection of liver transplantation in rats by inducing M2 polarization of Kupffer cells through the PI3K/Akt pathway.
机构信息
School of Physical Education Shanxi University, 030006 Taiyuan, China.
Research Center for Health Promotion of Children and Adolescents, Taiyuan Institute of Technology, No. 31, Xinlan Road, Jiancaoping District, 030008 Taiyuan, China.
出版信息
Cytokine. 2023 May;165:156085. doi: 10.1016/j.cyto.2022.156085. Epub 2023 Mar 30.
Liver transplantation (LT), a major therapy for end-stage liver disease, is often associated with acute rejection (AR). MicroRNAs (miRNAs) have been implicated in AR-related gene regulation. In this experiment, the mechanism of miR-27a-5p in AR of LT was studied. Allotransplantation model (LEW-BN) and syngeneic transplantation model (LEW-LEW) of rat orthotopic liver transplantation (OLT) were established. miR-27a-5p was overexpressed in recipient rats 28 days before LT to detect its effects on LT pathology, liver function, and survival time. Kupffer cells (KCs) were isolated and treated with lipopolysaccharide (LPS) and miR-27a-5p overexpression. miR-27a-5p overexpression reduced lymphocyte numbers around portal areas and central veins after LT and mitigated degeneration of epithelial cells of the bile duct. Expression levels of IL-10 and TGF-β1 were increased while IL-12 was decreased. Liver function damage was alleviated and the survival time of rats with LT was prolonged. miR-27a-5p induced M2 polarization of rats with AR after LT and LPS-treated KCs in vitro and promoted activation of the PI3K/Akt pathway in KCs. Inhibition of the PI3K/Akt pathway averted induction of miR-27a-5p on M2 polarization of KCs. Taken together, miR-27a-5p inhibited AR after LT in rats by inducing M2 polarization of KCs through the PI3K/Akt pathway.
肝移植（LT）是治疗终末期肝病的主要方法，常伴有急性排斥反应（AR）。microRNAs（miRNAs）参与了 AR 相关基因的调控。本实验研究了 miR-27a-5p 在 LT 中 AR 的作用机制。建立大鼠原位肝移植（OLT）同种异体移植模型（LEW-BN）和同基因移植模型（LEW-LEW）。在 LT 前 28 天，过表达受体大鼠中的 miR-27a-5p，以检测其对 LT 病理学、肝功能和生存时间的影响。分离并处理枯否细胞（KCs）用脂多糖（LPS）和 miR-27a-5p 过表达。LT 后，miR-27a-5p 过表达减少了门脉区和中央静脉周围的淋巴细胞数量，并减轻了胆管上皮细胞的变性。IL-10 和 TGF-β1 的表达水平增加，而 IL-12 减少。肝损伤减轻，LT 大鼠的生存时间延长。miR-27a-5p 诱导 LT 后 AR 大鼠和 LPS 处理的 KCs 体外 M2 极化，并促进 KCs 中 PI3K/Akt 通路的激活。抑制 PI3K/Akt 通路可避免 KCs 中 miR-27a-5p 对 M2 极化的诱导。综上所述，miR-27a-5p 通过 PI3K/Akt 通路诱导 KCs 的 M2 极化，抑制大鼠 LT 后的 AR。
Zotero 插件