Mechanism of Ropivacaine Inhibiting Hypoxia/reoxygenation-induced Alve-olar Epithelial Cell Injury

YIN Yalan; ZHONG Hui; BAO Lei; ZHAO Chunwu; LI Jinfeng; ZHOU Lu

doi:10.3969/j.issn.1002-3429.2023.07.011

Abstract：Objective To investigate the effects of Ropivacaine on oxidative stress,inflammatory response and ferrop-tosis in A549 cells induced by hypoxia/reoxygenation(H/R).Methods Human type Ⅱ alveolar epithelial cells A549 were divided into Control group(A549 cells did not receive any treatment),model group(H/R group)and Ropivacaine group(H/R combined with different concentrations of Ropivacaine).MTT assay was used to detect the effects of different concentra-tions of Ropivacaine on the activity of A549 cells,and TUNEL was used to analyze the effects of different concentrations of Ropivacaine on the apoptosis of A549 cells.The effects of different concentrations of Ropivacaine on oxidative stress,inflam-matory response and ferroptosis-related indicators in A549 cells were measured using relevant kits,and the effect of Ropiva-caine on the expression of related proteins was detected by Western blotting.Results Compared with Control group,A549 cells in H/R group had decreased viability,significantly increased apoptosis rate,and increased levels of malondialdehyde(MDA),interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),reactive oxygen species(ROS)and Fe2+.The levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were decreased,the expressions of FTH1 and GPX4 were significantly down-regulated,and the expressions of Tf,Keap1,Nrf2 and HO-1 were significantly up-regulated(P＜0.05,P＜0.01).Compared with H/R group,A549 cells in 5.00,10.00 and 20.00 μmol/L Ropivainine groups had increased viability,significantly decreased apoptosis rate,decreased SOD,GSH-Px,FTH1 and GPX4 expression,significant reversion of increased MDA,IL-6,IL-8,TNF-α,ROS,Fe2+ and Tf expression,decreased Keap1 protein expres-sion,and increased Nrf2 and HO-1 protein expression(P＜0.05,P＜0.01).Conclusion Ropivacaine plays a protective role in H/R-induced alveolar epithelial cell injury,which may be associated with the activation of Keap1-Nrf2/HO-1 signaling pathway.