海南医科大学学报2025，Vol.31Issue(12)：888-899,12.DOI:10.13210/j.cnki.jhmu.20241022.002
高压氧暴露调控HIF-1α对胶原诱导型关节炎小鼠骨破坏的机制研究
Effects of hyperbaric oxygen exposure regulating HIF-1α expression on bone destruction in mice with collagen-induced rheumatoid arthritis
摘要
Abstract
Objective:To explore the mechanism of hyperbaric oxygen(HBO)exposure in regulating hypoxia-inducible factor-1α(HIF-1α)expression that affects bone morphology in mice with type Ⅱ collagen-induced arthritis(CIA).Methods:A total of 40 male mice of DBA/1 were randomly divided into the normal group(NOR),the model group(CIA),the low-dose hyperbaric oxygen treatment group(HBO-L),and the high-dose hyperbaric oxygen treatment group(HBO-H),with 10 mice in each group.Except for the NOR group,mice of the other three groups were all treated with 2 immunizations of intradermal injection of type Ⅱcollagen-complete Freund's into the double hind paws and tail root to build the CIA model.The immunization was strengthen at 7 d interval.The mice in the HBO-L group and HBO-H groups were respectively exposed to 2.2 atmospheric absolute(ATA)pres-sure once a day for 7 d and once a day for 14 d after the second immunization was finished.The mice in the NOR group and the CIA group were all exposed to ordinary pressure air.Arthritis index(AI)was applied to evaluate the swelling degree of arthritis in mice.The level of HIF-1α、interleukin-1(IL-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)in the joint were exam-ined by qRT-PCR.The expression of HIF-1α protein was detected by Western blot(WB)and immunohistochemistry(IHC)in the joints.Hematoxylin-eosin(H&E)staining was applied to observe the pathological change of the joints.Pathological scoring of the joint tissue in each group was counted.Statistical data was compared among groups.Results:Compared to the CIA group,the degree of joint swelling and AI score in the HBO-L group and HBO-H group began to gradually decrease from the 11th day,and the differences were statistically significant(P<0.01).Compared to the HBO-L group,the degree of joint swelling and AI score in the HBO-H group began to show decreasing trend from the 15th day,and the differences were statistically significant(P<0.05).AI score decreased most significantly on the 21st day,and the differences were statistically significant(P<0.001).Com-pared to the CIA group,the mRNA expression levels of IL-1,IL-6,TNF-α,and HIF-1α in the joint tissues of the HBO-L group and HBO-H group gradually decreased,and the differences were statistically significant(P<0.05).Compared to the HBO-L group,the mRNA expression levels of IL-1,IL-6,TNF-α,and HIF-1α in the joint tissues of the HBO-H group showed decreas-ing trend,and the differences were statistically significant(P<0.01).Compared to the CIA group,the results of WB and IHC de-tection both showed that the relative expression levels of HIF-1α protein in the joint tissues of the HBO-L group and HBO-H group gradually decreased,and the differences were statistically significant(P<0.001).Compared to the HBO-L group,the rela-tive expression level of HIF-1α protein in the joint tissues of the HBO-H group showed decreasing trend,and the differences were statistically significant(P<0.001).Compared to the CIA group,the joint pathological scores of the HBO-L group and the HBO-H group gradually decreased,and the differences were statistically significant(P<0.001).Compared to the HBO-L group,the joint pathological scores in the HBO-H group showed decreasing trend,and the differences were statistically significant(P<0.001).H&E staining pathology showed that HBO improved inflammatory cell infiltration and reduced vascular proliferation,and the HBO-H group had better therapeutic effect.Conclusion:Hyperbaric oxygen exposure can significantly reduce joint swelling and effectively attenuate the inflammatory in the CIA model by improving joint hypoxia environment.The mechanism may be relat-ed to down-regulation of HIF-1α signaling pathway.The curative effect may be time-dependent.关键词
高压氧/HIF-1α/胶原诱导型关节炎/类风湿关节炎/抗炎Key words
Hyperbaric oxygen/Hypoxia-inducible factor-1α/Collagen-induced rheumatoid arthritis/Rheumatoid arthritis/Anti-inflammatory分类
医药卫生引用本文复制引用
李琴,殷诺,张辉..高压氧暴露调控HIF-1α对胶原诱导型关节炎小鼠骨破坏的机制研究[J].海南医科大学学报,2025,31(12):888-899,12.基金项目
This study was supported by the Shanghai Fengxian District Science and Technology Commission Project(20211606) 上海市奉贤区科委社会类科技发展基金项目(奉科20211606) （20211606）
