Role of miR-146a in bone marrow mesenchymal stem cells-induced reduction of acute lung injury in rats / 中华麻醉学杂志

ABSTRACT

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 intra-peritoneally injecting 5 mg∕kg lipopolysaccharide ( LPS) 0. 5 ml in anesthetized rats. Phosphate buffer solu-tion 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 a-nalysis 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 poly-merase chain reaction). Results Compared with group C, the pH value and PO2 were significantly de-creased, 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 aggrava-ted 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.