卡托普利对光气所致大鼠急性肺损伤的改善作用及其机制

doi:10.3969/j.issn.1004-616x.2026.02.002

癌变·畸变·突变 ›› 2026, Vol. 38 ›› Issue (2): 93-101.doi: 10.3969/j.issn.1004-616x.2026.02.002

• 论著 • 上一篇

卡托普利对光气所致大鼠急性肺损伤的改善作用及其机制

王常艳^1,2, 李佳威², 王会³, 陈金合⁴, 樊振鹏², 师敏婕^1,2, 李文丽², 张荣强¹

1. 陕西中医药大学公共卫生学院, 陕西咸阳 712046;
2. 空军军医大学军事预防医学系军事毒理学与防化医学教研室/陕西省自由基生物学与医学重点实验室/教育部特殊作业环境危害评估与防治重点实验室, 陕西西安 710032;
3. 西安医学院公共卫生学院, 陕西西安 710021;
4. 应急管理部化学品登记中心, 山东青岛 266071

收稿日期:2025-06-04 修回日期:2025-10-22 发布日期:2026-04-09
通讯作者: 李文丽, 张荣强
作者简介:王常艳,E-mail:17792032880@163.com。
基金资助:
国家自然科学基金(82373603); 陕西省教育厅重点实验室项目(2JS009)

Improvement effect of captopril on phosgene-induced acute lung injury in rats

WANG Changyan^1,2, LI Jiawei², WANG Hui³, CHEN Jinhe⁴, FAN Zhenpeng², SHI Minjie^1,2, LI Wenli², ZHANG Rongqiang¹

1. School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi;
2. Department of Military Toxicology and Chemical Defense Medicine, School of Military Preventive Medicine, Air Force Medical University/Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province/Key Laboratory of Environmental Hazard Assessment and Prevention of Special Operational Environment of Ministry of Education, Xi ' an 710032, Shaanxi;
3. School of Public Health, Xi ' an Medical University, Xi'an 710021, Shaanxi;
4. Chemical Registration Center of Emergency Management, Qingdao 266071, Shandong, China

Received:2025-06-04 Revised:2025-10-22 Published:2026-04-09

摘要/Abstract

摘要： 目的： 构建光气暴露诱导的SD大鼠急性肺损伤（ALI）模型，探究卡托普利对光气所致急性肺损伤的作用及其分子机制。方法： 将40只SD雄性大鼠随机分为对照组、光气染毒组、卡托普利组及光气与卡托普利联合组，每组各10只。光气染毒组和光气与卡托普利联合组经鼻腔动态吸入41 mg/m³的光气30 min，卡托普利组和光气与卡托普利联合组于染毒后立即腹腔注射5 mg/kg卡托普利。给药后观察24 h内大鼠存活情况。24 h后使用全身体积描记系统检测大鼠肺功能。然后处死大鼠，取肺组织，计算肺系数，采用HE染色评估肺组织病理损伤；BCA法检测肺泡灌洗液（BALF）中总蛋白浓度；ELISA法检测血清、BALF和肺匀浆中炎症因子IL-1β和TNF-α含量；用试剂盒检测超氧化物歧化酶（SOD）活性、谷胱甘肽过氧化物酶（GPx）活性和丙二醛（MDA）含量；免疫组织化学法和ELISA法检测肺组织血管紧张素转换酶（ACE）和血管紧张素Ⅱ（AngⅡ）的水平；TUNEL染色法观察肺组织中细胞凋亡情况；Western blot法检测肺组织凋亡相关蛋白Bcl-2的表达。结果： 与对照组相比，光气染毒组大鼠24 h存活率为80%，肺组织有出血点，HE染色呈现典型ALI病理改变；BALF、肺匀浆及血清中IL-1β和TNF-α水平均升高（P<0.01）;SOD和GPx活性降低（P<0.05或P<0.01）,MDA含量、ACE和Ang Ⅱ水平显著增加（P<0.01）；凋亡细胞密度显著增加且Bcl-2蛋白表达下降（均为P<0.01）。与光气染毒组相比，光气与卡托普利联合组大鼠生存率显著提高（P<0.05），且肺组织病理损伤减轻，肺功能明显恢复（P<0.01）；肺系数、BALF蛋白浓度显著降低（P<0.01），抗氧化酶SOD活性升高（P<0.05）;IL-1β、TNF-α含量、ACE活性和Ang Ⅱ含量均下降（P<0.05）；凋亡细胞数量减少（P<0.05）,Bcl-2蛋白表达明显上升（P<0.01）。结论： 卡托普利能够显著改善光气诱导的急性肺损伤，其机制涉及肺泡屏障修复、抗氧化防御增强及炎症抑制。本研究为光气中毒的临床治疗提供了实验依据。

关键词: 卡托普利, 光气, 急性肺损伤, 炎症, 氧化应激

Abstract: OBJECTIVE: To establish a phosgene-induced acute lung injury（ALI） model in SD rats and to investigate mechanisms for improvement effect of captopril on ALI rats. METHODS: Forty male SD rats were randomly divided into control,phosgene poisoning（Phos）,Captopril（CAP） and combined groups with phosgene and captopril（Phos+CAP）, with ten rats in each group. Rats dynamically inhaled 41 mg/m³ phosgene for 30 minutes in Phos and Phos+CAP groups and received intraperitoneal injection with 5 mg/kg Captopril immediately after phosgene poisoning in CAP and Phos+CAP groups. Survival rates of the rats were determined within 24 hours after administration. Lung function of the rats was measured using a whole-body plethysmography（WBP）system after 24 hours. Rat lung tissues were collected to measure the lung coefficient. HE staining of lung tissues was performed to assess pathological damage. Total protein concentration was determined in bronchoalveolar lavage fluid（BALF） by BCA method. Inflammatory factors including IL-1β and TNF-α were detected by ELISA in serum, BALF and lung homogenate. Activities of superoxide dismutase（SOD） and glutathione peroxidase（GPx）,content of malondialdehyde（MDA） were measured by kits. Levels of Angiotensin-converting enzyme（ACE）and angiotensin Ⅱ（Ang Ⅱ） were determined by immunohistochemistry and ELISA. Apoptosis in lung tissues was observed by TUNEL staining. Expression of Bcl-2 in lung tissue was detected by Western blotting. RESULTS: Compared with the control group, the 24 h survival rate of rats in the phosgene exposure group was 80%.Pulmonary hemorrhage spots were observed,and HE staining showed typical pathological changes of acute lung injury. Levels of IL-1β and TNF-α in bronchoalveolar lavage fluid,lung homogenate,and serum were elevated（P<0.01）. Activities of SOD and GPx were decreased（P<0.05）,while MDA content as well as ACE and Ang Ⅱ levels were significantly increased（P<0.01）. Apoptotic cell density was markedly increased（P < 0.01） along with reduced expression of Bcl-2 protein（P<0.01）. Compared with Phos group,levels of IL-1β and TNF-α and the activity of angiotensin-converting enzyme（ACE） and content of angiotensin Ⅱ（Ang Ⅱ） were significantly decreased in the Phos+CAP group（P<0.05）. The number of apoptotic cells decreased（P<0.05）,and Bcl-2 protein expression declined（P<0.01）. CONCLUSION: Captopril significantly alleviated acute lung injury which was induced by phosgene. Alleviation mechanisms may be related to alveolar barrier repair, enhanced antioxidant defense and inflammation suppression. This study provides experimental evidence for a clinical approach of phosgene poisoning.

Key words: captopril, phosgene, acute lung injury, inflammation, oxidative stress

中图分类号:

王常艳, 李佳威, 王会, 陈金合, 樊振鹏, 师敏婕, 李文丽, 张荣强. 卡托普利对光气所致大鼠急性肺损伤的改善作用及其机制[J]. 癌变·畸变·突变, 2026, 38(2): 93-101.

WANG Changyan, LI Jiawei, WANG Hui, CHEN Jinhe, FAN Zhenpeng, SHI Minjie, LI Wenli, ZHANG Rongqiang. Improvement effect of captopril on phosgene-induced acute lung injury in rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(2): 93-101.

参考文献

[1] 孙慕涵,王钰越,张勃旭,等.间充质干细胞在光气致肺损伤治疗中的应用展望[J].空军军医大学学报, 2024, 45(5):582-586.
[2] NICHOLSON-ROBERTS T C. Phosgene use in World War 1and early evaluations of pathophysiology[J]. J R Army Med Corps, 2019, 165(3):183-187.
[3] LU Q Y, HUANG S Y, MENG X Y, et al. Mechanism of phosgene-induced acute lung injury and treatment strategy[J].Int J Mol Sci, 2021, 22(20):10933.
[4] GUTCH M, JAIN N, AGRAWAL A, et al. Acute accidental phosgene poisoning:Figure 1[J]. BMJ Case Rep, 2012, 2012:bcr1120115233.
[5] LI W L, LIU F F, WANG C, et al. Novel insights into phosgene-induced acute lung injury in rats:role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis[J]. Toxicol Sci, 2013, 131(2):612-628.
[6] LU Q Y, HUANG S Y, MENG X Y, et al. Mechanism of phosgene-induced acute lung injury and treatment strategy[J].Int J Mol Sci, 2021, 22(20):10933.
[7] 郭晓洁,刘鹏晖,龙子,等.氧化应激致自噬在光气诱导的急性肺损伤中的作用[J].癌变·畸变·突变, 2023, 35(5):325-333, 340.
[8] LI W L, PAULUHN J. Phosgene-induced acute lung injury(ALI):differences from chlorine-induced ALI and attempts to translate toxicology to clinical medicine[J]. Clin Transl Med,2017, 6(1):19.
[9] AGGARWAL S, AHMAD I, LAM A, et al. Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema[J]. JCI Insight, 2018, 3(21):e120694.
[10] 闫冬,赵赞梅,马青变.炎症反应在光气致急性肺损伤/急性呼吸窘迫综合征中的研究进展[J].中国急救医学, 2024, 44(2):164-170.
[11] AGGARWAL S, LAM A, BOLISETTY S, et al. Heme attenuation ameliorates irritant gas inhalation-induced acute lung injury[J]. Antioxid Redox Signal, 2016, 24(2):99-112.
[12] HOLMES W W, KEYSER B M, PARADISO D C, et al.Conceptual approaches for treatment of phosgene inhalationinduced lung injury[J]. Toxicol Lett, 2016, 244:8-20.
[13] 张帆,王成彬.局部血管紧张素系统在急性肺损伤中的作用研究进展[J].临床检验杂志:电子版, 2015, 4(2):850-858.
[14] TAN W S D, LIAO W P, ZHOU S, et al. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases[J]. Curr Opin Pharmacol, 2018, 40:9-17.
[15] 何晓静,邱枫,肇丽梅.卡托普利对急性肺损伤大鼠的保护作用[J].中国医院药学杂志, 2010, 30(18):1583-1586.
[16] 霍艳萍,焦安德,刘玉梅,等.卡托普利通过抑制氧化应激损伤和减轻炎症反应对冠脉微栓塞大鼠发挥心肌保护作用[J].中国病理生理杂志, 2019, 35(9):1614-1619.
[17] LI Y C, ZENG Z, LI Y C, et al. Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced lung injury by regulating the balance between angiotensin-converting enzyme and angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase activation[J]. Shock, 2015, 43(4):395-404.
[18] HE G H, YU W H, LI H W, et al. Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response[J]. Eur J Pharmacol, 2023, 957:176017.
[19] LIU H M, GUO Y N. Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL[J]. Asian Pac J Trop Med, 2014, 7(11):905-908.
[20] 方青,高荣,高英杰,等.急性肺损伤动物模型的研究现状[J].中国畜牧兽医, 2010, 37(5):50-54.
[21] SAĞLAM E, SEHIRLI A O, OZDAMAR E N, et al. Captopril protects against burn-induced cardiopulmonary injury in rats[J]. Ulus Travma Acil Cerrahi Derg, 2014, 20(3):151-160.
[22] 华楚信,张昊.静滴卡托普利治疗婴幼儿肺炎临床观察[J].中国医院药学杂志, 1994, 14(2):61-62.
[23] 唐冬梅.卡托普利对非酒精性脂肪肝的治疗效果及对其氧化应激的影响观察[J].中国实用医药, 2020, 15(12):125-126.
[24] 李佳威,郭晓洁,师敏婕,等.雾化吸入NaClO致小鼠肺损伤模型的构建及机制研究[J].癌变·畸变·突变, 2024, 36(4):281-287, 297.
[25] 谭晶今,张雁林.急性呼吸窘迫综合征相关生物标志物研究进展[J]. 2025(10):745-754.
[26] PENG W J, QI H, ZHU W S, et al. Lianhua Qingke ameliorates lipopolysaccharide-induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis[J]. Pulm Circ, 2023, 13(4):e12295.
[27] 王渊学,丁永刚,马宏武.血管紧张素类抗高血压药物在高血压治疗中的创新应用与发展趋势[J].中国医药科学,2025, 15(14):25-31.
[28] 张波,刘树芬,张劭夫,等.血清血管紧张素转换酶活性变化对急性肺损伤患者预后的判断价值[J].临床荟萃, 1994(21):962-963.
[29] 朱钰珊,彭学容,范苏苏,等.炎症与氧化应激在急性肺损伤中的作用研究进展[J].生物医学, 2024, 14(1):48-55.
[30] 陈涛,何文华,朱萱,等.熊果酸对血管紧张素II诱导肝星状细胞内NADPH氧化酶的活化及下游信号通路的影响[J].上海交通大学学报:医学版, 2015, 35(1):17-22.
[31] LI Y C, ZENG Z, CAO Y M, et al. Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways[J]. Sci Rep, 2016, 6:27911.

卡托普利对光气所致大鼠急性肺损伤的改善作用及其机制

Improvement effect of captopril on phosgene-induced acute lung injury in rats

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	蔡晓彤, 谢冰梦, 周莉, 李仰康, 黄裔腾, 彭琳. 炎症营养复合指标与I型子宫内膜癌预后的相关性分析[J]. 癌变·畸变·突变, 2026, 38(1): 15-21.
[2]	王曹赞, 谢清华, 花福增, 陈潇湘, 赵威, 刘瑞, 海春旭, 张晓迪. 己酮可可碱在急性肺损伤中的应用进展[J]. 癌变·畸变·突变, 2025, 37(6): 498-500,506.
[3]	赵红峥, 叶奕良, 马鸣. 全身免疫炎症指数在非小细胞肺癌患者临床辅助诊断及进展监测中的意义[J]. 癌变·畸变·突变, 2025, 37(5): 369-374.
[4]	杜彦艳, 李洁, 周文烨, 马鸣, 崔雯瑄, 王振达, 姚影珍. 多指标联合检测对多发性骨髓瘤早期肾损伤患者的诊断及预后评估价值[J]. 癌变·畸变·突变, 2025, 37(5): 389-392,399.
[5]	陈怡如, 王丽, 武鑫悦, 赵艳. 铁超载加重非酒精性脂肪肝病过程中线粒体自噬的作用及其机制[J]. 癌变·畸变·突变, 2025, 37(4): 319-323,329.
[6]	曹猛, 龙子, 于卫华, 孔德钦, 吴昊, 刘江正, 王钊, 刘瑞, 张倩, 海春旭. 硫芥中毒机制及救治药物研究进展[J]. 癌变·畸变·突变, 2025, 37(4): 341-345.
[7]	高天, 王振, 曹猛, 李飞, 师敏婕, 刘江正, 刘瑞, 吴昊, 海春旭. 咖啡酸苯乙酯对光气诱导大鼠急性肺损伤的保护作用及其机制[J]. 癌变·畸变·突变, 2025, 37(2): 113-120.
[8]	李宏伟, 刘江正, 孔德钦, 孙明继. 四氧化二氮诱导急性肺损伤的机制及救治研究进展[J]. 癌变·畸变·突变, 2025, 37(2): 166-169,174.
[9]	刘佳文, 乐乐, 梁徐睿, 张志豪, 张涛. 多聚唾液酸在肿瘤治疗中的研究进展[J]. 癌变·畸变·突变, 2025, 37(2): 170-174.
[10]	曹猛, 王振, 高天, 于卫华, 刘江正, 孔德钦, 吴昊, 龙子, 王钊, 刘瑞, 海春旭. 咖啡酸苯乙酯对硫芥诱导小鼠急性肺损伤的保护作用研究[J]. 癌变·畸变·突变, 2025, 37(1): 8-15.
[11]	师敏婕, 李佳威, 郭晓洁, 王常艳, 樊振鹏, 刘江正, 李文丽, 孔德钦, 辛宝. 雾化吸入糜烂性毒剂2-氯乙基乙基硫醚对小鼠肺功能的影响[J]. 癌变·畸变·突变, 2025, 37(1): 27-32,38.
[12]	邓紫丰, 师敏婕, 詹天豪, 马耀, 刘建豪, 马丞飞, 赵昱舜, 李嘉, 刘江正, 孔德钦. 沉默信息调节因子1在急性肺损伤中作用的研究进展[J]. 癌变·畸变·突变, 2025, 37(1): 72-74,80.
[13]	何改花, 范珊红, 李文丽. α1-抗胰蛋白酶的功能及其与肺部疾病关系的研究进展[J]. 癌变·畸变·突变, 2024, 36(6): 502-505.
[14]	师敏婕, 李嘉, 邓紫丰, 詹天豪, 刘建豪, 赵昱舜, 李文丽, 刘江正, 孔德钦. 盐酸右美托咪定对2-氯乙基乙基硫醚致人支气管上皮细胞损伤的保护作用及机制[J]. 癌变·畸变·突变, 2024, 36(5): 342-348,358.
[15]	郭采妮, 刘璟, 张玉龙, 丁黎, 付步芳. 硅凝胶乳房植入物相关疾病的研究进展[J]. 癌变·畸变·突变, 2024, 36(5): 412-416.