Effect of bone marrow-derived mesenchymal stem cells on mTOR signaling pathways in lung tissues of rats with acute lung injury

Abstract

Objective To evaluate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on mammalian target of rapamycin (mTOR) signaling pathways in lung tissues of rats with acute lung injury (ALI). Methods Healthy pathogen-free adult male Sprague-Dawley rats were selected, and the BMSCs were obtained and cultured in vitro.One hundred and five healthy clean adult male Sprague-Dawley rats, weighing 170-190 g, were divided into 5 groups (n=21 each) using a random number table: control group (group C), PBS group, group ALI, ALI plus BMSC group (group ALI+ BMSCs), and ALI plus phosphate buffer solution (PBS) group (group ALI+ PBS). Group C received no treatment.PBS 0.5 ml was injected via the tail vein in group PBS.Lipopolysaccharide (LPS, 0.5 ml) 5 mg/kg was intraperitoneally injected to establish the model of ALI in group ALI.BMSCs (0.5 ml) 1×104 cells/ml were injected via the tail vein after intraperitoneal injection of LPS in group ALI+ BMSCs.PBS 0.5 ml was injected via the tail vein after intraperitoneal injection of LPS in group ALI+ PBS.Arterial blood samples were collected for blood gas analysis at 6, 24 and 48 h after injection of BMSCs.Lungs were then removed for determination of wet/dry weight ratio (W/D ratio) and expression of mTOR, nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) in lung tissues (by Western blot) and for examination of the pathologic changes of lungs tissues (using haematoxylin and eosin staining). Results Compared with group C, pH value and PaO2 were significantly decreased, PaCO2 and W/D ratio were increased, and the expression of mTOR, NF-κB and TNF-α was up-regulated at each time point in ALI, ALI+ BMSCs and ALI+ PBS groups (P<0.05). Compared with group ALI, pH value and PaO2 were significantly increased, PaCO2 and W/D ratio were decreased, the expression of mTOR, NF-κB and TNF-α was down-regulated at each time point (P<0.05), and the pathologic changes of lungs tissues were significantly attenuated in group ALI+ BMSCs. Conclusion The mechanism by which BMSCs reduce ALI may be associated with inhibiting mTOR signaling pathways in lung tissues of rats. Key words: Mesenchymal stem cell transplantation; Receptor-interacting protein serine-threonine kinases; Respiratory distress syndrome, adult