解放军医学院学报2023，Vol.44Issue(9)：1001-1009,9.DOI:10.12435/j.issn.2095-5227.2023.082
内皮抑制素抑制RhoA/ROCK信号通路减轻脂多糖诱导的小鼠急性肺损伤实验研究
Endostatin attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting RhoA/ROCK signaling pathway
摘要
Abstract
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.关键词
内皮抑制素/急性肺损伤/RhoA/ROCK信号通路/细胞因子/炎症反应Key words
endostatin/acute lung injury/RhoA/ROCK signaling pathway/cytokine/inflammatory reaction分类
医药卫生引用本文复制引用
岳渊,张涛,柳朝阳,张鹏霞,肖漓,张娟..内皮抑制素抑制RhoA/ROCK信号通路减轻脂多糖诱导的小鼠急性肺损伤实验研究[J].解放军医学院学报,2023,44(9):1001-1009,9.基金项目
首都卫生发展科研专项(首发2022-2-5092) （首发2022-2-5092）
黑龙江省卫生健康委科研课题(20210202040058) （20210202040058）
