Min Fang, Gao Fengying, Li Qian, Liu Zhenwei
Department of Obstetrics, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China.
Department of Respiratory Medicine, Shanghai Jiangong Hospital, Shanghai 200083, P.R. China.
Mol Med Rep. 2015 Apr;11(4):2387-96. doi: 10.3892/mmr.2014.3025. Epub 2014 Dec 1.
The aim of the present study was to evaluate the therapeutic effects of human umbilical cord mesenchymal stem cells (uMSCs) in the presence of angiotensin‑converting enzyme 2 gene (ACE2; ACE2‑uMSCs) on bleomycin (BLM)‑induced lung injury and pulmonary fibrosis in mice. A total of 100 male C57BL/6 mice were divided at random into five groups (n=20) as follows: Control group, BLM group, ACE2 group, uMSC group and ACE2‑uMSC group. At 7, 14 and 28 days post‑treatment, the following parameters were evaluated in lung tissue: Oxidation indexes [malondialedehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and oxidized glutathione (GSSG)]; fibrosis factors [tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ and transforming growth factor (TGF)‑β]; inflammatory cytokines [Interleukin (IL)‑1, IL‑2, IL‑6 and IL‑10]; ACE2 gene expression; hydroxyproline and collagen type 1 messenger RNA (mRNA) concentration; as well as matrix metalloproteinase (MMPs; 2 and 9) and tissue inhibitor of metalloproteinase (TIMP)1‑4 expression. ACE2‑uMSC injection following bleomycin pretreatment significantly alleviated lung injury in mice. In addition, treatment with ACE2‑uMSCs demonstrated a stronger therapeutic effect than ACE2‑ or uMSC treatment alone, indicated by decreased expression of MDA, GSSG, TNF‑α, IFN‑γ, TGF‑β, IL‑1, IL‑2, IL‑6, collagen type 1 mRNA, MMPs and TIMPs as well as hydroxyproline concentration, and upregulation of SOD, GSH and ACE2 and IL‑10. In conclusion, the results of the present study demonstrated that ACE2 and uMSCs had a synergistic therapeutic effect on bleomycin‑induced acute lung injury.
本研究的目的是评估在存在血管紧张素转换酶2基因（ACE2；ACE2 - 脐带来源间充质干细胞）的情况下，人脐带来源间充质干细胞（uMSCs）对博来霉素（BLM）诱导的小鼠肺损伤和肺纤维化的治疗效果。总共100只雄性C57BL/6小鼠被随机分为五组（n = 20），如下：对照组、BLM组、ACE2组、uMSC组和ACE2 - uMSC组。在治疗后7天、14天和28天，对肺组织评估以下参数：氧化指标[丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）]；纤维化因子[肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和转化生长因子（TGF）-β]；炎性细胞因子[白细胞介素（IL）-1、IL - 2、IL - 6和IL - 10]；ACE2基因表达；羟脯氨酸和I型胶原信使核糖核酸（mRNA）浓度；以及基质金属蛋白酶（MMPs；2和9）和金属蛋白酶组织抑制剂（TIMP）1 - 4表达。博来霉素预处理后注射ACE2 - uMSC可显著减轻小鼠的肺损伤。此外，与单独使用ACE2或uMSC治疗相比，ACE2 - uMSC治疗显示出更强的治疗效果，表现为MDA、GSSG、TNF -α、IFN -γ、TGF -β、IL - 1、IL - 2、IL - 6、I型胶原mRNA、MMPs和TIMPs的表达以及羟脯氨酸浓度降低，SOD、GSH、ACE2和IL - 10上调。总之，本研究结果表明，ACE2和uMSCs对博来霉素诱导的急性肺损伤具有协同治疗作用。
