Role of miR-146a in bone marrow mesenchymal stem cells-induced reduction of acute lung injury in rats

Objective To evaluate the role of miR-146a in bone marrow mesenchymal stem cells (BMSCs)-induced reduction of acute lung injury (ALI) in rats. Methods A total of 105 clean-grade healthy male Wistar rats, weighing 170-190 g, were divided into 5 groups (n=21 each) using a random number table method: control group (group C), phosphate buffer solution group (group P), group ALI, BMSC group (group B) and BMSC plus miR-146a inhibitor group (group BM). ALI was induced by intraperitoneally injecting 5 mg/kg lipopolysaccharide (LPS) 0.5 ml in anesthetized rats.Phosphate buffer solution 0.5 ml was injected via the tail vein in group P. In group B, 1×104 cells/ml BMSC 0.5 ml was injected via the tail vein after establishing the model.In group BM, miR-146a inhibitor 50 mg/kg was injected via the tail vein after establishing the model, and 2 h later 1×104 cells/ml BMSC 0.5 ml was injected via the tail vein.Group C received no treatment.Blood samples were obtained from the abdominal aorta for blood gas analysis at 6, 24 and 48 h after injection of BMSC (T1-3), the chest was immediately opened, and the lung tissues were obtained for microscopic examination of pathologic changes and for determination of the wet/dry lung weight ratio (W/D ratio), expression of IRAK-1, nuclear factor kappa B (NF-κB) and interleukin-6 (IL-6) (by Western blot) and expression of miR-146a and IRAK-1 mRNA (by quantitative real-time polymerase chain reaction). Results Compared with group C, the pH value and PO2were significantly decreased, PCO2 and W/D ratio were increased, and the expression of IRAK-1, NF-κB, IL-6 and miR-146a was up-regulated at each time point (P<0.05), and the pathological changes of lung tissues were aggravated in ALI, B and BM groups.Compared with group P, the pH value and PO2 were significantly decreased, PCO2 and W/D ratio were increased, and the expression of IRAK-1, NF-κB, IL-6 and miR-146a was up-regulated at each time point (P<0.05), and the pathological changes of lung tissues were aggravated in ALI, B and BM groups.Compared with group ALI, the pH value and PO2 were significantly increased, PCO2 and W/D ratio were decreased, and the expression of IRAK-1, NF-κB, IL-6 and miR-146a was down-regulated at each time point (P<0.05), and the pathological changes of lung tissues were attenuated in group B. Compared with group B, the pH value and PO2 were significantly decreased, PCO2 and W/D ratio were increased, and the expression of IRAK-1, NF-κB, IL-6 and miR-146a was up-regulated at each time point (P<0.05), and the pathological changes of lung tissues were aggravated in group BM. Conclusion miR-146a is involved in BMSCs-induced reduction of ALI in rats. Key words: MicroRNAs; Mesenchymal stem cell transplantation; Acute lung injury