Wang Xishuai, Zhao Shiyu, Lai Junhui, Guan Weijun, Gao Yang
Department of Animal Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
College of P.E and Sport, Beijing Normal University, Beijing 100193, China.
Int J Mol Sci. 2021 Dec 22;23(1):99. doi: 10.3390/ijms23010099.
Mesenchymal stem cell (MSC) intervention has been associated with lung protection. We attempted to determine whether mouse gingival-derived mesenchymal stem cells (GMSCs) could protect against bleomycin-induced pulmonary fibrosis.
Mice were divided into three groups: control (Con), bleomycin (Bl), and bleomycin + MSCs (Bl + MSCs). Mice were treated with 5 mg/kg bleomycin via transtracheal instillation to induce pulmonary fibrosis. We assessed the following parameters: histopathological severity of injury in the lung, liver, kidney, and aortic tissues; the degree of pulmonary fibrosis; pulmonary inflammation; pulmonary oedema; profibrotic factor levels in bronchoalveolar lavage fluid (BALF) and lung tissue; oxidative stress-related indicators and apoptotic index in lung tissue; and gene expression levels of IL-1β, IL-8, TNF-α, lysophosphatidic acid (LPA), lysophosphatidic acid receptor 1 (LPA1), TGF-β, matrix metalloproteinase 9 (MMP-9), neutrophil elastase (NE), MPO, and IL-10 in lung tissue.
GMSC intervention attenuated bleomycin-induced pulmonary fibrosis, pulmonary inflammation, pulmonary oedema, and apoptosis. Bleomycin instillation notably increased expression levels of the IL-1β, IL-8, TNF-α, LPA, LPA1, TGF-β, MMP-9, NE, and MPO genes and attenuated expression levels of the IL-10 gene in lung tissue, and these effects were reversed by GMSC intervention. Bleomycin instillation notably upregulated MDA and MPO levels and downregulated GSH and SOD levels in lung tissue, and these effects were reversed by GMSC intervention. GMSC intervention prevented upregulation of neutrophil content in the lung, liver, and kidney tissues and the apoptotic index in lung tissue.
GMSC intervention exhibits anti-inflammatory and antioxidant capacities. Deleterious accumulation of neutrophils, which is reduced by GMSC intervention, is a key component of bleomycin-induced pulmonary fibrosis. GMSC intervention impairs bleomycin-induced NE, MMP-9, LPA, APL1, and TGF-β release.
间充质干细胞（MSC）干预与肺保护作用有关。我们试图确定小鼠牙龈来源的间充质干细胞（GMSC）是否能预防博来霉素诱导的肺纤维化。
将小鼠分为三组：对照组（Con）、博来霉素组（Bl）和博来霉素+间充质干细胞组（Bl+MSCs）。通过气管内滴注5mg/kg博来霉素处理小鼠以诱导肺纤维化。我们评估了以下参数：肺、肝、肾和主动脉组织的组织病理学损伤严重程度；肺纤维化程度；肺部炎症；肺水肿；支气管肺泡灌洗液（BALF）和肺组织中的促纤维化因子水平；肺组织中的氧化应激相关指标和凋亡指数；以及肺组织中白细胞介素-1β（IL-1β）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）、溶血磷脂酸（LPA）、溶血磷脂酸受体1（LPA1）、转化生长因子-β（TGF-β）、基质金属蛋白酶9（MMP-9）、中性粒细胞弹性蛋白酶（NE）、髓过氧化物酶（MPO）和白细胞介素-10（IL-10）的基因表达水平。
GMSC干预减轻了博来霉素诱导的肺纤维化、肺部炎症、肺水肿和细胞凋亡。博来霉素滴注显著增加了肺组织中IL-1β、IL-8、TNF-α、LPA、LPA1、TGF-β、MMP-9、NE和MPO基因的表达水平，并降低了肺组织中IL-10基因的表达水平，而GMSC干预逆转了这些作用。博来霉素滴注显著上调了肺组织中的丙二醛（MDA）和MPO水平，并下调了谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平，而GMSC干预逆转了这些作用。GMSC干预阻止了肺、肝和肾组织中中性粒细胞含量的上调以及肺组织中凋亡指数的升高。
GMSC干预具有抗炎和抗氧化能力。GMSC干预减少了中性粒细胞的有害积聚，中性粒细胞积聚是博来霉素诱导的肺纤维化的关键组成部分。GMSC干预抑制了博来霉素诱导的NE、MMP-9、LPA、APL1和TGF-β的释放。
