Activation of adenosine A2B receptor attenuates sepsis-induced acute lung injury and pulmonary microvascular endothelial inflammation injury
WANG Huixia
AN Youzhong
Abstract：Objective To analyse the effect of the activation of adenosine A2B receptor(A2BR)on sepsis-induced acute lung injury(ALI)and to explore its regulatory role in pulmonary microvascular endothelial inflammation injury.Methods(1)A total of 24 Sprague-Dawley(SD)rats were randomly divided into sham operation group(sham group),ALI model group(ALI group),A2BR agonist BAY60-6583 intervention group(ALI+BAY group),and A2BR inhibitor PSB1115 intervention group(ALI+PSB group),with 6 rats in each group.The rats were sacrificed 24 hours after mod-eling,and their lung tissues were collected.Lung injury score(Smith score)was obtained under light microscopy,and lung wet/dry mass ratio(W/D)was calculated.Alveolar fluid clearance(AFC)rate was detected by Evans Blue stai-ning.The levels of inflammatory factors in lung tissues including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1 β(IL-1β)were detected by enzyme-linked immunosorbent assay(ELISA).(2)TNF-α-induced human pulmonary microvascular endothelial cells(HPMECs)injury model was used.The control group,TNF-α group,BAY group,PSB group,BAY+TNF-α group and PSB+TNF-α group were set up.After 24 hours of cell culture,fluores-cein isothiocyanate(FITC)-albumin assay was used to detect the monolayer permeability of HPMECs in each group,and the levels of IL-1 β,intercellular adhesion molecule-1(ICAM-1),vascular endothelial-cadherin(VE-cadherin)and angiopoietins(ANGPT)expressions were detected by Werstern blot.Results Compared with the sham group,the ALI group showed significantly increased Smith score,lung W/D,and levels of TNF-α,IL-6 and IL-1 β in lung tissues,and showed significantly decreased AFC.Compared with the ALI group,the ALI+BAY group showed significantly decreased Smith score,lung W/D,and levels of TNF-α,IL-6 and IL-1 β in lung tissues,and showed significantly increased AFC.However,the ALI+PSB group showed the opposite results.In the TNF-α-induced HPMECs injury model,compared with the control group,the TNF-α group showed the increased levels of IL-1 β and ICAM-1 expressions,and the increased monolayer permeability of HPMECs,and the decreased levels of VE-cadherin and ANGPT expressions.Compared with the TNF-α group,the BAY+TNF-α group showed the decreased levels of IL-1 β and ICAM-1 expressions and the decreased monolayer permeability of HPMECs,and the increased levels of VE-cadherin and ANGPT expressions.However,pre-treatment with PSB1115 could reverse the above phenomenon.The differences among the above groups were statistically significant(P＜0.05).Conclusion Activation of A2BR can attenuate sepsis-induced ALI and exert protective effects by reducing pulmonary microvascular endothelial inflammation,reducing permeability and promoting angiogenesis pathways.
Keywords：Adenosine A2B receptor(A2BR)SepsisAcute lung injury(ALI)Human pulmonary microvascular endothelial cells(HPMECs)Inflammation
Publication Date：2024-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 138-144 )