• Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P. R. China;
PANG Liewen, Email: huashan_heart@sina.cn
Export PDF Favorites Scan Get Citation

Objective To investigate whether treatment of rivaroxaban, an approved oral direct coagulation factor Xa inhibitor, attenuates functional changes in LPS -induced acute lung injury (ALI) mouse.Methods C57BL/6 mice were randomly divided into PBS group, N-LPS group, L-LPS group, and H-LPS group. In the C57BL/6 mice being fed chow containing 0.2 mg/g or 0.4 mg/g rivaroxaban for 10 days (L-LPS group and H-LPS group), plasma concentration and coagulation indices were measured. Next, the role of rivaroxaban in ALI by using mice fed by rivaroxaban was studied in a murine ALI model induced by direct intratracheal injection lipopolysaccharides (LPS). Lung injury by histopathological scoring, micro computed tomography, pulmonary edema, inflammatory cell recruitment and activity of inflammatory cytokines in lung tissue or bronchoalveolar lavage fluid (BALF) were assessed. Western blot and immunohistochemistry were performed to examine expression of multiple proteins, including myeloperoxidase, protease-activatedreceptor 2 (PAR-2) and nuclear factor kappa B (NF-κB).Results The increased plasma concentration of rivaroxaban and the prolonged prothrombin time were displayed in the mice with rivaroxaban treatment. Rivaroxaban treatment groups showed significant reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the LPS positive control (P<0.05). Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels, in addition to total protein and Evans blue concentration were all significantly reduced in BALF from the mice treated with the chow containing rivaroxaban. Administration of rivaroxaban ameliorated ALI with concomitant reductions in the expression of PAR-2 and proinflammatory cytokines. LPS-induced PAR-2 increase and NF-κB activation were also suppressed by rivaroxaban in lung tissues. Furthermore, rivaroxaban inhibited the phosphorylation levels of P65 in ALI.Conclusions The results demonstrate that rivaroxaban effectively attenuates LPS-induced inflammatory responses by noncoagulative pathway in ALI. The beneficial effects are associated with the decreased phosphorylation of NF-κB pathways and the reduced expression of PAR-2.

Citation: SHI Meng, HUANG Jiechun, SUN Xiaotian, WANG Fangrui, CHU Xianglin, JIANG Rongrong, WANG Yiqing, PANG Liewen. The effect of direct coagulation factor Xa inhibitor on acute lung injury progression induced by endotoxin in mice. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(4): 369-376. doi: 10.7507/1671-6205.201810048 Copy

  • Previous Article

    Air-liquid interface culture of mouse tracheal-bronchial epithelial cells
  • Next Article

    Analysis of project application and funding by National Natural Science Foundation of China in the field of respiratory medicine from 2010 to 2017