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骨髓间充质干细胞对脂多糖诱导的急性肺损伤小鼠的早期治疗作用
引用本文:邰文琳,董昭兴,张丹丹,王殿华. 骨髓间充质干细胞对脂多糖诱导的急性肺损伤小鼠的早期治疗作用[J]. 南方医科大学学报, 2012, 32(3): 283-290. DOI: 44-1627/R.20120307.1116.004
作者姓名:邰文琳  董昭兴  张丹丹  王殿华
作者单位:1.昆明医学院第二附属医院 检验科,云南昆明650101;昆明医学院药学院暨云南省天然药物药理重点实验室,云南昆明650031;2.昆明医学院第二附属医院 呼吸内科,云南昆明,650101;3.昆明医学院药学院暨云南省天然药物药理重点实验室,云南昆明,650031
基金项目:Innovation,Foundation,of,Kunming,Medical,University,for,Doctoral,Candidates,Joint,Natural,Science,Foundation,of,Yunnan,Province,and,Kunming,Medical,University(2011FB194)昆明医学院博士研究生创新基金,云南省科技厅-昆明医学院联合专项基金
摘    要:目的 观察经尾静脉输注的骨髓间充质干细胞(MSCs)对脂多糖(LPS)诱导的急性肺损伤小鼠的早期治疗作用.方法 采用密度梯度单个核细胞分离培养法分离纯化骨髓间充质干细胞,传至第4代时观察细胞形态、流式细胞仪检测细胞表面标志,定向诱导检测分化能力后备用.36只小鼠随机分为对照组,PBS治疗组,MSC治疗组.对照组气管内滴注生理盐水50 μl,PBS和MSC治疗组气管内滴注LPS制备急性肺损伤模型.造模后lh后经尾静脉输注MSC5× 106(MSCs治疗组)或PBS 100 μl(PBS治疗组或对照组).24h后处死小鼠,留取标本检测肺组织病理形态学、肺组织湿干重比(W/D)、支气管肺泡灌洗液(BALF)中中性粒细胞数、蛋白含量、细胞因子水平和肺组织中的MPO表达量.结果 与对照组比较,PBS治疗组肺组织病理损伤严重,BALF中中性粒细胞数、蛋白含量、TNF-α、IL-6和IL-10水平、肺组织中的MPO含量及肺组织湿干重比均显著升高.与PBS治疗组比较,MSCs治疗组肺组织病理损伤程度减轻,BALF中中性粒细胞数、蛋白含量、TNF-α、IL-6水平、肺组织中的MPO含量及肺组织湿干重比均显著降低,但仍高于对照组水平,IL-10水平显著高于PBS治疗组和对照组.结论MSCs移植在LPS诱导的急性肺损伤早期阶段可有效改善肺组织病理损伤,减轻肺部炎症反应,降低肺水肿程度,这种治疗作用不依赖于MSCs移植后在肺内的定植数量.

关 键 词:骨髓间充质干细胞  脂多糖  急性肺损伤

Therapeutic effect of intravenous bone marrow-derived mesenchymal stem cell transplantation on early-stage LPS-induced acute lung injury in mice
TAI Wenlin,DONG Zhaoxing,ZHANG Dandan,WANG Dianhua. Therapeutic effect of intravenous bone marrow-derived mesenchymal stem cell transplantation on early-stage LPS-induced acute lung injury in mice[J]. Journal of Southern Medical University, 2012, 32(3): 283-290. DOI: 44-1627/R.20120307.1116.004
Authors:TAI Wenlin  DONG Zhaoxing  ZHANG Dandan  WANG Dianhua
Affiliation:1Departement of Clinical Laboratory,2Department of Respiratory Diseases,Second Affiliated Hospital of Kunming Medical University,Kunming 650101,China;3School of Pharmacy and Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming 650031,China
Abstract:Objective To investigate the effect of intravenous bone marrow-derived mesenchymal stem cell(MSC) transplantation for early intervention of lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice.Methods Thirty-six mice were randomized into control group,PBS-treated ALI group,and MSC-treated ALI group.In the latter two groups,mouse models of ALI were established by intranasal instillation of LPS,and 1 h later,the 4th passage of MSCs isolated from the bone marrow of mice or PBS were administered via the tail vein.The histological findings,lung wet/dry(W/D) weight ratio,neutrophil count and protein and cytokine contents in the bronchoalveolar lavage fluid(BALF),and myeloperoxidase(MPO) level in the lung tissue were analyzed at 24 h after MSC administration.Engraftment of MSCs in the recipient lung was determined by fluorescent PKH26 staining and flow cytometry.Results Compared with the control group,PBS-treated ALI group showed significantly higher protein levels,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and neutrophil count in the BALF and MPO content in the lung tissue,with also severe damage of lung histology.MSCs administration significantly reduced the lung W/D weight ratio,the levels of protein,TNF-α,IL-6 and neutrophil count in the BALF and MPO content in the lung tissue,and obviously lessened the lung injury 24 h after the transplantation.MSC administration also significantly increased the level of IL-10 in the BALF.Conclusion Intravenous MSC transplantation can effectively improve the lung histology,attenuate the inflammatory response,reduce pulmonary edema in the early stage of LPS-induced ALI in mice,and such effects are independent of MSC engraftment in the lungs.
Keywords:bone marrow-derived mesenchymal stem cells  lipopolysaccharide  acute lung injury
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