Elchaninov Andrey, Vishnyakova Polina, Kuznetsova Maria, Gantsova Elena, Kiseleva Viktoria, Lokhonina Anastasiya, Antonova Maria, Mamedov Aiaz, Soboleva Anna, Trofimov Dmitry, Fatkhudinov Timur, Sukhikh Gennady
Laboratory of Growth and Development, Avtsyn Research Institute of Human Morphology of FSBI "Petrovsky National Research Centre of Surgery", Moscow, Russia.
Histology Department, Medical Institute, Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.
Front Cell Dev Biol. 2023 Sep 7;11:1241819. doi: 10.3389/fcell.2023.1241819. eCollection 2023.
The role of the immune system in liver repair is fundamentally complex and most likely involves the spleen. The close connection between the two organs via the portal vein enables delivery of splenic cytokines and living cells to the liver. This study evaluates expression of inflammation-related genes and assesses the dynamics of monocyte-macrophage and lymphocyte populations of the spleen during the recovery from 70% hepatectomy in mice. The study used the established mouse model of 70% liver volume resection. The animals were sacrificed 24 h, 72 h or 7 days post-intervention and splenic tissues were collected for analysis: Clariom™ S transcriptomic assay, immunohistochemistry for proliferation marker Ki-67 and macrophage markers, and flow cytometry for lymphocyte and macrophage markers. The loss and regeneration of 70% liver volume affected the cytological architecture and gene expression profiles of the spleen. The tests revealed significant reduction in cell counts for Ki-67+ cells and CD115+ macrophages on day 1, Ly6C + cells on days 1, 3 and 7, and CD3CD8 cytotoxic lymphocytes on day 7. The transcriptomic analysis revealed significant activation of protease inhibitor genes , and and decreased expression of cell cycle regulatory genes on day 1, mirrored by inverse dynamics observed on day 7. Splenic homeostasis is significantly affected by massive loss in liver volume. High levels of protease inhibitors indicated by increased expression of corresponding genes on day 1 may play an anti-inflammatory role upon reaching the regenerating liver via the portal vein. Leukocyte populations of the spleen react by a slow-down in proliferation. A transient decrease in the local CD115+ and Ly6C+ cell counts may indicate migration of splenic monocytes-macrophages to the liver.
免疫系统在肝脏修复中的作用从根本上来说十分复杂，而且很可能涉及脾脏。这两个器官通过门静脉紧密相连，使得脾脏细胞因子和活细胞能够输送至肝脏。本研究评估了炎症相关基因的表达，并评估了小鼠70%肝切除术后恢复过程中脾脏内单核细胞-巨噬细胞和淋巴细胞群体的动态变化。该研究采用了已建立的70%肝脏体积切除小鼠模型。在干预后24小时、72小时或7天处死动物，并收集脾脏组织进行分析：Clariom™ S转录组分析、增殖标志物Ki-67和巨噬细胞标志物的免疫组织化学分析，以及淋巴细胞和巨噬细胞标志物的流式细胞术分析。70%肝脏体积的丧失和再生影响了脾脏的细胞学结构和基因表达谱。检测显示，第1天Ki-67+细胞和CD115+巨噬细胞的细胞计数显著减少，第1天、第3天和第7天Ly6C +细胞减少，第7天CD3CD8细胞毒性淋巴细胞减少。转录组分析显示，第1天蛋白酶抑制剂基因 、 显著激活，细胞周期调控基因表达降低，第7天观察到相反的动态变化。肝脏体积的大量丧失显著影响了脾脏的内环境稳定。第1天相应基因表达增加所表明的高水平蛋白酶抑制剂，可能在通过门静脉到达再生肝脏时发挥抗炎作用。脾脏的白细胞群体通过增殖减缓做出反应。局部CD115+和Ly6C+细胞计数的短暂减少可能表明脾脏单核细胞-巨噬细胞迁移至肝脏。
