Department of Gastroenterology and Hepatology, Tianjin Medical University, General Hospital, Tianjin, China.
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Hebei Medical University, Hebei, China.
Biomed Res Int. 2019 Jan 6;2019:5756189. doi: 10.1155/2019/5756189. eCollection 2019.
Splenectomy can improve liver function and survival in patients with autoimmune hepatitis (AIH) and liver cirrhosis. We investigated the underlying mechanism in a mouse model of concanavalin A- (ConA-) induced liver fibrosis.
We used ConA to induce immune liver fibrosis in BALB/c mice. Splenectomy was performed alone or with the administration of dexamethasone (DEX). Changes in blood and liver tissues were evaluated.
Mice treated with ConA for 7 weeks developed advanced liver fibrosis, while splenectomy suppressed liver fibrosis. Although the populations of macrophages/monocytes and M1 macrophages decreased after splenectomy, the inflammatory factors associated with M2 macrophages increased after splenectomy. Furthermore, the population of circulating CD11bLy6C myeloid-derived suppressor cells (MDSCs) increased after splenectomy. After ConA treatment, elevated levels of activated and total NF-kBp65/p50 combined with DNA were observed in hepatic tissues. In contrast, the levels of NF-B p65/p50 decreased after splenectomy.
Splenectomy may promote the polarization of CD11bLy6C MDSCs and the differentiation of M2 macrophages while restricting the level of NF-B p65-p50 heterodimers. These factors may suppress the progression of liver fibrosis.
脾切除术可改善自身免疫性肝炎（AIH）和肝硬化患者的肝功能和生存率。我们在刀豆蛋白 A （ConA）诱导的肝纤维化小鼠模型中研究了其潜在机制。
我们使用 ConA 诱导 BALB/c 小鼠免疫性肝纤维化。单独或联合地塞米松（DEX）进行脾切除术。评估血液和肝组织的变化。
用 ConA 处理 7 周的小鼠发生了晚期肝纤维化，而脾切除术则抑制了肝纤维化。尽管脾切除术后巨噬细胞/单核细胞和 M1 巨噬细胞的数量减少，但与 M2 巨噬细胞相关的炎症因子在脾切除术后增加。此外，循环 CD11bLy6C 髓源抑制细胞（MDSC）的数量在脾切除术后增加。在用 ConA 处理后，在肝组织中观察到活化和总 NF-kBp65/p50 与 DNA 的结合水平升高。相比之下，脾切除术后 NF-B p65/p50 的水平降低。
脾切除术可能通过促进 CD11bLy6C MDSC 的极化和 M2 巨噬细胞的分化，同时限制 NF-B p65-p50 异二聚体的水平，从而抑制肝纤维化的进展。
