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间充质干细胞通过抑制肝中性粒细胞和巨噬细胞浸润以及氧化应激来减轻小鼠的酒精性肝炎。

Mesenchymal stem cells reduce alcoholic hepatitis in mice via suppression of hepatic neutrophil and macrophage infiltration, and of oxidative stress.

机构信息

Public Health Institute of Kunming Medical University, Kunming, Yunnan province, China.

Gastroenterology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.

出版信息

PLoS One. 2020 Feb 11;15(2):e0228889. doi: 10.1371/journal.pone.0228889. eCollection 2020.

Abstract

Mesenchymal stem cells (MSCs) are a population of pluripotent cells that have been tested for the treatment of many inflammatory diseases. It remains unclear whether MSCs were effective in treating mice with alcoholic hepatitis (AH) and its underlying mechanism. In the present study, MSCs were isolated from bone marrow of 4-6 week-old C57BL/6N male mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) transplantation of MSCs or saline were performed in mice on day 10. Blood samples and hepatic tissues were harvested on day 11. Biochemical, liver histological and flow cytometric analyses were performed. Compared to the control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic neutrophil and macrophage infiltration (P<0.001), which were markedly reduced by i.p. transplantation of MSCs (P<0.01). Compared to the control mice, the hepatic glutathione (GSH) was prominently lower in the AH mice (P<0.001), which was markedly enhanced after i.p. injection of MSCs (P<0.001). MSCs were effective for the treatment of AH mice, which might be associated with their ability in inhibiting hepatic neutrophil and macrophage infiltration, and alleviating oxidative stress.

摘要

间充质干细胞(MSCs)是一种多能细胞,已被用于治疗多种炎症性疾病。目前尚不清楚 MSCs 是否对治疗酒精性肝炎(AH)及其潜在机制有效。在本研究中,我们从 4-6 周龄 C57BL/6N 雄性小鼠的骨髓中分离出 MSCs。通过慢性 binge 乙醇喂养 10 天诱导雌性小鼠发生 AH。在第 10 天,对小鼠进行 MSC 或生理盐水的腹腔内(i.p.)移植。在第 11 天采集血液样本和肝组织。进行生化、肝组织学和流式细胞术分析。与对照组小鼠相比,AH 小鼠的肝/体重比、血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)、肝总胆固醇(TC)、甘油三酯(TG)、丙二醛(MDA)、肝中性粒细胞和巨噬细胞浸润显著增加(P<0.001),而腹腔内注射 MSCs 可显著降低这些指标(P<0.01)。与对照组小鼠相比,AH 小鼠的肝谷胱甘肽(GSH)明显降低(P<0.001),而腹腔内注射 MSCs 可显著增强 GSH(P<0.001)。MSCs 对 AH 小鼠有效,这可能与其抑制肝中性粒细胞和巨噬细胞浸润以及减轻氧化应激的能力有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12e3/7012433/dbd5004bfd51/pone.0228889.g001.jpg

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