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Home > Archive>Volume 28, Issue 5, 2020 >618-626. DOI:10. 3969 / j.issn.1005-4847. 2020. 05. 005
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Angiotensin-converting enzyme 2 attenuates acute lung injury induced by limb ischemia reperfusion in mice via regulation of pulmonary renin-angiotensin system
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1.School of Public Health, North China University of Science and Technology, Tangshan 063210, China. 2.Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210. 3.School of Basic Medical Sciences, Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Clinical and Basic Research on Chronic Diseases, North China University of Science and Technology, Tangshan 063210. 4.Academic Affairs Office, North China University of Science and Technology, Tangshan 063210

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    Abstract:

    Objective To explore the protective potential and mechanism of angiotensin-converting enzyme II (ACE2) in acute lung injury (ALI) induced by limb ischemia reperfusion in mice. Methods Male wild-type and ACE2 transgenic mice (overexpression of ACE2) Institute of Cancer Research mice were randomly divided into six groups (n =18): wild control group (Control), wild model group (Model), ACE2 control group (ACE2 + Control), ACE2 model group (ACE2 + Model), ACE2 model + A779 group (ACE2 + Model + A779), and ACE2 model + MLN-4760 group (ACE2 + Model + MLN-4760). ALI models were established using rubber band ligation of the bilateral hind limb roots (ischemia for 2 h and reperfusion for 4 h). Lung histological changes were observed using hematoxylin and eosin (HE) staining. Lung water content and pulmonary permeability were indicated by the organ coefficient, wet-to-dry weight ratio, cell numbers, and protein concentration in the bronchoalveolar lavage fluid (BALF). Enzyme-linked immunosorbent assay was used to determine the concentrations of BALF interleukin ( IL) - 6, tumor necrosis factor ( TNF) - α, and lung angiotensin II (Ang II) / angiotensin-(1-7) [Ang-(1-7)]. Quantitative real-time polymerase chain reaction was used to analyze mRNA expression of ACE/ ACE2, and western blot used to quantify the protein expression of ACE/ ACE2 and AT1 / Mas receptors. Results Compared with the wild model group, overexpression of ACE2 attenuated lung lesions ( HE staining and lung injury score), reduced alveolar capillary permeability (organ coefficient, wet-to-dry weight ratio, BALF cell numbers, protein concentration), improved the expression profiles of inflammatory cytokines (IL-6 and TNF-α) in the BALF, and (particularly) reversed pulmonary renin-angiotensin system imbalance. Moreover, these effects were abrogated by MLN-4760 (a specific ACE2 inhibitor) and A779 ( a specific Mas receptor antagonist). Conclusions The findings indicate that ACE2 can ameliorate the imbalance of the pulmonary renin-angiotensin system and the ALI via the ACE2-Ang- (1-7)-Mas axis.

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  • Received:July 13,2020
  • Online: November 25,2020
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