目的:观察经尾静脉输注骨髓间充质干细胞培养上清液(MSCs CdM)对脂多糖(LPS)诱导的小鼠急性肺损伤的治疗作用及其机制。方法:采用全骨髓培养法分离纯化骨髓间充质干细胞,传至第3代时观察细胞形态,流式细胞术检测细胞表面标志,并且收集上清液用超滤离心管进行离心。30只BALB/c小鼠随机分为对照组、LPS模型组和MSCs CdM治疗组。对照组腹腔内注射生理盐水(0.01mL/g),LPS组和MSCs CdM治疗组腹腔内注射LPS(5mg/kg,0.01mL/g)制备急性肺损伤模型。造模1h后经尾静脉输注MSCs CdM(MSCs CdM治疗组)或生理盐水(LPS组或对照组)300曲。6h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)中蛋白含量、血清及BALF中细胞因子水平和肺组织中髓过氧化物酶(MPO)的活性。结果:与对照组比较,LPS处理后肺组织病理损伤严重,BALF中蛋白、血清肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)含量、肺组织中MPO活性及肺组织湿干重比均显著升高。与LPS组比较,MSCs CdM治疗组肺组织病理损伤程度减轻,BALF中蛋白、血清TNF-α和IL-6含量、肺组织中MPO活性及肺组织湿干重比均显著降低,而BALF中自细胞介素10(IL-10)和角质细胞生长因子(KGF)水平显著高于LPS组和对照组。结论:骨髓间充质干细胞培养上清液可有效减轻LPS诱导的急性肺损伤,其作用机制可能与其调节肺部TNF-α、IL-6、IL-10和KGF的水平有关。
AIM: To explore the effects of bone marrow-derived mesenchymal stem cells-conditioned medium (MSCs CdM) on lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Lung injury was induced in mice by intraperitoneal injection of LPS. The mice were given a tail vein injection of MSCs CdM or normal saline 1 h after LPS ad- ministration. The mice were killed by an intraperitoneal injection of pentobarbital 6 h after LPS injection for either bron- choalveolar lavage fluid (BALF) and serum collection or lung histological analysis. RESULTS: Compared with control group, the BALF levels of protein, interleukin-10 (IL-10) and keratinocyte growth factor (KGF), the serum levels of tumor necrosis factor α (TNF-α) and IL-6, and the myeloperoxidase (MOP) activity in the lung tissues were significantly higher in LPS group, and severe pathological damages in the lung tissues were also observed. Treatment with MSCs CdM significantly reduced the BALF prtein level, the seum TNF-α and IL-6 levels and the lung MPO activity, and attenuated the lung pathological damages, but further increased the levels of IL-10 and KGF in the BALF. CONCLUSION: Treatment with MSCs CdM attenuates the lung injuries induced by LPS, which may be via regulating the expression of TNF-α, IL-6, IL-10 and KGF.