Abstract:

Objective To construct a rat model of early pulmonary fibrosis following lipopolysaccharide (LPS)-induced acute lung injury and observe the change trend in major members of renin-angiotensin-system angiotensin Ⅱ type 1 receptor (AT1R) and Mas receptor during lung injury process. Methods A rat model of early pulmonary fibrosis following acute lung injury was built by three intermittent injections of LPS into the abdomen and airway. Rats were sacrificed 3, 7, 14, and 21 d after last injection. Lung tissues and blood samples were harvested. The histomorphological changes in lung tissues were observed with H-E and Masson staining. The plasma TGF-β level was measured with ELISA kits. The mRNA and protein expressions of AT1R and Mas receptors in lung tissues were detected with RT-qPCR and Western blotting, respectively. Results The main presentation of histomorphological changes in lung tissues was inflammatory response at day 3 after LPS injections. The inflammation was reduced 7 d after LPS injections and the normal morphology of lung tissues was damaged. Masson staining revealed increased collagen protein deposition and plasma TGF-β level (P<0.01), which resulted in early pulmonary fibrosis. In addition, with the development of LPS-induced pulmonary fibrosis, the mRNA expression of AT1R did not change significantly, but the protein expression of AT1R markedly increased on day 14 and 21. The mRNA expression of Mas in lung tissues increased gradually and was 15 folds higher than that in the control group on day 21, while the protein expression of Mas significantly decreased to 30% of that in the control group on day 14 and 21 (P<0.01). Conclusion Repeated LPS injections can effectively construct the rat model of early pulmonary fibrosis following acute lung injury. The expressions of AT1R and Mas receptors show opposite changes with the development of pulmonary fibrosis.

Key words: LPS, acute lung injury, early pulmonary fibrosis, AT1R, Mas