新斯的明与山莨菪碱联合应用对肺型氧中毒的保护作用及其机制的研究  

Protective effect and mechanisms of neostigmine in combination with anisodamine against pulmonary oxygen toxicity

作　　者：张广雨 杜晶[2] 刘梦珍 朱丹妮 闫慧 刘冲 ZHANG Guangyu;DU Jing;LIU Mengzhen;ZHU Danni;YAN Hui;LIU Chong(School of Pharmacy,Naval Medical University,Shanghai 200433,China;School of Pharmacy,Jining Medical University,Jining 276826,China)

机构地区：[1]海军军医大学药学系,上海200433 [2]济宁医学院药学院,山东济宁276826

出　　处：《药学实践与服务》2024年第10期433-438,444,共7页Journal of Pharmaceutical Practice and Service

摘　　要：目的高压氧(HBO)诱导的肺型氧中毒尚无有效的防治措施。该研究旨在阐明新斯的明(NEO)与山莨菪碱(ANI)联合(简称新斯莨菪碱)应用对肺型氧中毒的作用并初步探讨其机制。方法将C57BL/6小鼠暴露于2.5 ATA 99.9%氧气6 h制备肺型氧中毒模型,对照组小鼠给予生理盐水腹腔注射,治疗组小鼠给予ANI(25 mg/kg,腹腔注射)和NEO(50μg/kg,腹腔注射),暴露结束后取肺组织进行检测。HE染色观察肺组织的病理损伤情况;伊文思蓝染色通过检测肺通透性以及测定肺湿/干比及肺泡灌洗液中的蛋白含量来衡量肺损伤的严重程度;同时测定肺组织中炎症因子、氧化应激指标以及铁含量变化情况。结果与正常组相比,模型组的肺损伤程度显著加重,肺通透性、肺湿/干比以及肺泡灌洗液中蛋白含量同步增加;肺组织中促炎因子IL-1β、IL-6、TNF-α、IFN-γ的mRNA水平显著增加,抑炎因子IL-4、TGF-β明显降低;氧化指标MDA显著升高、抗氧化指标GSH则显著降低;铁含量升高,铁死亡的标志物GPX4表达量增加,而给予新斯莨菪碱治疗后能明显逆转上述变化。结论新斯莨菪碱对肺型氧中毒具有保护作用,可能通过激活胆碱能抗炎通路,从而抑制炎症和氧化应激的发生,进而减少了肺组织中游离铁的含量,最终抑制细胞铁死亡。Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen,frequently occurs in specialized operations,without any current effective prevention or treatment measures.To elucidate the impact and mechanism of neostigmine(NEO)in combination with anisodamine(ANI)(neoscopolamine)on pulmonary oxygen toxicity.Methods The animal model of pulmonary oxygen poisoning was established.C57BL/6 mice were exposed to 2.5 ATA 99.9%oxygen for 6 h.The control group mice were injected with normal saline ip,while the treatment group mice received injections of ANI(25 mg/kg,ip)and NEO(50μg/kg,ip).Lung tissues were collected and stained with HE to observe any pathological injuries after exposure.Evans blue stain was utilized to identify lung permeability,wet/dry lung ratio,and protein concentration in the bronchoalveolar lavage fluid(BALF)to assess the lung injury’s severity.The modifications in inflammatory factors,oxidative stress indicators,and iron content in lung tissue were assessed.Results The results showed that the 2.5 ATA 99.9%oxygen-exposed group experienced a significant worsening of lung injury,as well as increased lung permeability,lung wet/dry ratio,and protein content in alveolar lavage fluid when compared to the control group.Moreover,mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γin the lung tissue of the model group were significantly elevated,while the levels of anti-inflammatory cytokines IL-4 and TGF-βwere significantly reduced.The oxidative index MDA also significantly increased,while the antioxidant index GSH significantly decreased.Additionally,the expression of GPX4,a marker of ferroptosis,increased with an increase in iron content.Neoscopolamine treatment successfully reversed those effects.Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning.Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway,thereby reducing the content of free iron in lung tissue and finally inh

关 键 词：高压氧 肺型氧中毒 新斯莨菪碱 炎症 氧化应激 

分 类 号：R965[医药卫生—药理学]