摘要目的 评价骨髓间充质干细胞(BMSCs)对大鼠急性肺损伤(ALI)时转化生长因子β1/Smad(TGF-β1/Smad)信号通路的影响.方法 清洁级健康雄性SD大鼠,4～5周龄,体重100～ 120 g,体外培养BMSCs.选取健康清洁级成年雄性SD大鼠84只,4周龄,体重170～190 g,采用随机数字表法分为4组(n=21):对照组(C组)、ALI组、ALI+BMSCs组和ALI+PBS组.腹腔注射5 mg/kg LPS 0.5 ml制备ALI模型.ALI+ BMSCs组腹腔注射LPS后尾静脉注射1×104个/ml BMSCs 0.5 ml(用PBS溶解);ALI+PBS组腹腔注射LPS后尾静脉注射PBS 0.5 ml.分别于注射BMSCs后6、24和48 h时,采集动脉血样测定血气分析,测定肺组织湿重/干重(W/D)比值,采用HE染色观察肺组织病理学结果,采用Western blot法测定肺组织TGF-β1、Smad2和Smad3的表达.结果 与C组比较,ALI组、ALI+BMSCs组和ALI+ PBS组各时点PaO2降低,PaCO2和肺组织W/D比值升高,肺组织TGF-β1、Smad2和Smad3表达上调(P＜0.05),肺组织病理学损伤加重.与ALI组比较,ALI+BMSCs组各时点PaO2升高,PaCO2和肺组织W/D比值降低,肺组织TGF-β1、Smad2和Smad3表达下调(P＜0.05),肺组织病理学损伤减轻.结论 BMSCs减轻大鼠ALI的机制可能与抑制TGF-β1/Smad信号通路有关.

abstractsObjective To evaluate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on transforming growth factor-β1 (TGF-β1)/Smad signaling pathway during acute lung injury (ALI) in rats.Methods Healthy clean-grade adult male Sprague-Dawley rats,aged 4-5 weeks,weighing 100-120 g,were selected,and BMSCs were prepared and cultured in vitro.Eighty-four healthy clean-grade adult male Sprague-Dawley rats,aged 4 weeks,weighing 170-190 g,were selected and divided into 4 groups (n=21 each) using a random number table method:control group (group C),group ALI,ALI plus BMSCs group (group ALI + BMSCs),and ALI plus phosphate buffer solution (PBS)group (group ALI+PBS).ALI was induced by intraperitoneally injecting 5 mg/kg lipopolysaccharide 0.5 ml in anesthetized rats.In group ALI+BMSCs,1×104 cells/ml BMSCs 0.5 ml (in PBS) was injected via the tail vein after intraperitoneal injection of lipopolysaccharide.PBS 0.5 ml was injected via the tail vein after intraperitoneal injection of lipopolysaccharide in group ALI+PBS.Arterial blood samples were collected at 6,24 and 48 h after injecting BMSCs for blood gas analysis and for determination of wet to dry weight ratio (W/D ratio),pathological changes (using haematoxylin and eosin staining),and expression of TGF-β1,Smad2 and Smad3 in lung tissues (by Western blot).Results Compared with group C,PaO2 was significantly decreased,PaCO2 and W/D ratio were increased,the expression of TGF-β1,Smad2 and Smad3 in lung tissues was up-regulated (P＜0.05),and the pathological changes of lung tissues were accentuated in ALI,ALI+BMSCs and ALI+PBS groups.Compared with group ALI,PaO2 was significantly increased,PaCO2and W/D ratio were decreased,the expression of TGF-β1,Smad2 and Smad3 in lung tissues was down-regulated (P＜0.05),and the pathological changes of lung tissues were significantly reduced in group ALI+BMSCs.Conclusion The mechanism by which BMSCs mitigates ALI may be associated with inhibiting TGF-β1/Smad signaling pathway in rats.