重庆医学2025，Vol.54Issue(12)：2766-2773,8.DOI:10.3969/j.issn.1671-8348.2025.12.009
4-苯基丁酸对机械通气相关性肺损伤小鼠肺组织内质网应激的影响
Effect of 4-phenylbutyric acid on endoplasmic reticulum stress in lung tissue of mice with ventilator-induced lung injury
摘要
Abstract
Objective To investigate the effect of the endoplasmic reticulum stress(ERS)inhibitor 4-phenylbutyric acid(4-PBA)on ERS in lung tissue of mice with ventilator-induced lung injury(VILI).Meth-ods Twenty-four specific pathogen-free male BALB/C mice were randomly divided into the normal control group(NC group),the VILI group,and the VILI+4-PBA treatment group(VILI+4-PBA group)by random number table method,with 8 mice in each group.VILI was induced by high-tidal-volume mechanical ventila-tion.The VILI+4-PBA group received 4-PBA(200 mg/kg)intraperitoneally 1 hour before ventilation.The levels of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-1β and cell adhesion molecule-1(ICAM-1)in serum and lung tissue were detected by ELISA.The level of vascular endothelial growth factor(VEGF)in bronchial BALF was detected by ELISA,and the total protein concentration was detected by BCA.HE stai-ning was used to observe the morphological changes of lung tissue.The mRNA expression levels of glucose-regulated protein 78(GRP78)and C/EBP homologous protein(CHOP)in lung tissue were detected by qPCR.Western blot was used to detect nuclear factor-κB(NF-κB),hypoxia-inducible factor-1 α(HIF-1α),and ERS-related proteins[GRP78,CHOP,X-box binding protein-1(XBP-1),activating transcription factor-6(ATF-6),ATF-4,phosphorylated-eukaryotic translation initiation factor 2α(p-eIF2α)]in lung tissue expres-sion level.Results Compared with the NC group,the levels of IFN-γ,TNF-α,IL-1β and ICAM-1 in the serum and lung tissue of mice in the VILI group were significantly increased(P<0.05),the lung tissue injury was obvious,and the levels of VEGF and total protein in BALF were significantly increased(P<0.05).The mR-NA and protein expression levels of GRP78 and CHOP in lung tissue were significantly increased(P<0.05),and the protein expression levels of NF-κB,HIF-1α,XBP-1,ATF-6,ATF-4 and p-eIF2α in lung tissue were significantly increased(P<0.05).Compared with the VILI group,the levels of IFN γ,TNF-α,IL-1β,and ICAM-1 in the serum and lung tissue of mice in the VILI+4-PBA group decreased significantly(P<0.05),lung tissue injury improved significantly,and the levels of VEGF and total protein in BALF decreased signifi-cantly(P<0.05).The mRNA and protein expression levels of GRP78 and CHOP in lung tissue decreased significantly(P<0.05),and the protein expression levels of NF-κB,HIF-1α,XBP-1,ATF-4,ATF-6 and p-eIF2α in lung tissue decreased significantly(P<0.05).Conclusion ERS plays an important role in VILI.4-PBA may alleviate VILI by suppressing ERS,possibly through modulation of NF-κB or HIF-1α expression.关键词
4-苯基丁酸/机械通气相关性肺损伤/内质网应激/炎症因子/缺氧诱导因子-1αKey words
4-phenylbutyric acid/ventilator-induced lung injury/endoplasmic reticulum stress/inflam-matory factors/hypoxia-inducible factor-1α分类
医药卫生引用本文复制引用
ZHANG Xueping,CHEN Lin,XU Junping,XIE Wan,YU Tianxing,ZHANG Geng,LIN Xin..4-苯基丁酸对机械通气相关性肺损伤小鼠肺组织内质网应激的影响[J].重庆医学,2025,54(12):2766-2773,8.基金项目
福州市科技计划项目(2022-S-022) （2022-S-022）
福建省自然科学基金项目(2023J011499) （2023J011499）
福建省重点专科建设项目(20220102). （20220102）
