Background Acute lung injury (ALI) is an acute pneumonia disease caused by a variety of incentives. At present, there is no effective prevention and treatment method. Endostatin (ES) can specifically inhibit the proliferation and migration of vascular endothelial cells, which is widely used in tumor therapy, but its role in acute lung injury remains unclear.
Objective To investigate the effect of ES on lipopolysaccharide (LPS) -induced acute lung injury in mice and its possible mechanism.
Methods A total of 36 male C57BL/6 mice were randomly divided into control group, LPS group (model group), ES intervention group A (LPS + 1 mg/kg ES for 6 h), ES intervention group B (LPS + 1 mg/kg ES for 12 h), ES intervention group C (LPS + 5 mg/kg ES for 6 h), and ES intervention group D (LPS + 5 mg/kg ES for 12 h), with 6 mice in each group. In the LPS group, LPS solution was delivered to the lungs of mice according to the dose of 15 mg/kg through the lung liquid quantitative atomization device, and the acute lung injury models of mice were established after LPS injection for 24 hours. In the control group, the same volume of saline was delivered in the same way at the same time point for 24 hours. In the ES intervention groups, mice were intraperitoneally injected with different doses of ES (1 mg/kg or 5 mg/kg) for 6 h or 12 h at 24 h after LPS stimulation. The morphological changes of lung tissues were observed. The changes of lung coefficient were measured. Hematoxylin-eosin (HE) staining was used for pathological examination. Serum levels of vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay (ELISA). The contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and bronchoalveolar lavage fluid (BALF) were detected by flow cytometry. Apoptosis of lung cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The expression levels of Ras homolog gene family member A (RhoA) and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1) in lung tissues of mice in each group were detected by Western blot (WB).
Results Compared with the control group, the lung coefficient, the lung injury score and the number of apoptotic cells in lungs of LPS group all increased (all P＜0.01). The level of VEGF in serum, the contents of TNF-α and IL-6 in serum and BALF, and the expression levels of RhoA and ROCK1 in lung tissues also increased (all P＜0.05). Compared with LPS group, the inflammatory infiltration, pulmonary interstitial edema and alveolar structure destruction were alleviated in ES intervention group D. The lung injury score, the lung coefficient and the number of apoptotic cells in lungs decreased in ES intervention group D (all P＜0.01); The levels of TNF-α, IL-6 and VEGF in serum decreased (all P＜0.01), and the expression levels of RhoA and ROCK1 in lungs also decreased (P ＜0.05).
Conclusion Endostatin can alleviate LPS-induced acute lung injury in mice and reduce cell apoptosis in lung tissues. The function of endostatin in reducing pulmonary capillary endothelial cell permeability and inflammatory response may be related to the inhibition of RhoA/ROCK signaling pathway.
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