三氮脒通过激活ACE2减轻光气诱导的大鼠急性肺损伤  

Diminazene aceturate alleviates phosgene-induced acute lung injury in rats by activating ACE2

作　　者：李宏伟 何改花 刘江正 于卫华 孔德钦 龙子 刘瑞 李文丽 LI Hongwei;HE Gaihua;LIU Jiangzheng;YU Weihua;KONG Deqin;LONG Zi;LIU Rui;LI Wenli(Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine&Ministry-of-Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment,Department of Military Toxicology and Chemical Defense Medicine,School of Military Preventive Medicine,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]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

出　　处：《空军军医大学学报》2022年第3期331-335,共5页Journal of Air Force Medical University

基　　金：国家自然科学基金(82173544)。

摘　　要：目的探讨血管紧张素转换酶2(ACE2)激动剂三氮脒(DIZE)对光气诱导的大鼠急性肺损伤(ALI)的作用。方法40只SD雄性大鼠随机分为四组:空气对照组、光气染毒组、DIZE对照组、DIZE干预组。光气染毒6 h后收集血清和肺组织。HE染色肺组织切片观察肺形态学改变;免疫荧光染色法检测肺组织8-OH-dG表达。ELISA法测定各组大鼠血清ACE2、血管紧张素(Ang)Ⅱ、Ang-(1-7)、IL-6和TNF-α的含量。结果与空气对照组相比,光镜下可见光气染毒组大鼠肺泡结构破坏、炎细胞浸润;ACE2、Ang-(1-7)含量降低,AngⅡ含量升高;肺组织免疫荧光8-OH-dG表达升高;血清中IL-6、TNF-α含量明显升高(P<0.05)。与光气染毒组相比,光镜下DIZE干预组大鼠肺组织的炎细胞明显减少;ACE2、Ang-(1-7)含量升高,AngⅡ含量降低;肺组织免疫荧光8-OH-dG表达降低,血清中IL-6、TNF-α含量降低(P<0.05)。结论DIZE可能通过上调ACE2的表达减轻光气诱导的大鼠ALI,这为光气中毒的救治提供了新思路。Objective To investigate the effect of angiotensin-converting enzyme 2(ACE2)agonist diminazene aceturate(DIZE)on phosgene-induced acute lung injury(ALI)in rats.Methods Forty male SD rats were randomly divided into four groups:air control group,phosgene-poisoned group,DIZE control group,and DIZE intervention group.Serum and lung tissues were collected 6 h after exposure to phosgene.The morphological changes of lung tissue sections were observed by HE staining;the expression of 8-OH-dG in lung tissues was detected by immunofluorescence staining,and the levels of serum ACE2,angiotensin(Ang)Ⅱ,Ang-(1-7),IL-6 and TNF-αwere determined by ELISA.Results Compared with the air control group,the phosgene-poisoned group showed destroyed alveolar structure and inflammatory cell infiltration;ACE2 and Ang-(1-7)decreased,and AngⅡincreased;the expression of immunofluorescence 8-OH-dG in lung tissues increased;and the levels of IL-6 and TN F-αin serum went up significantly(P<0.05).Compared with the phosgene-poisoned group,the inflammatory cells in lung tissues of the DIZE intervention group under light microscope were significantly reduced;ACE2 and Ang-(1-7)increased,and AngⅡdecreased;the expression of immunofluorescence 8-OH-dG in lung tissues decreased;and the levels of IL-6 and TNF-αin serum went down(P<0.05).Conclusion DIZE may reduce phosgene-induced ALI by up-regulating the expression of ACE2,which provides a new idea for the treatment of phosgene poisoning.

关 键 词：光气 肺损伤 血管紧张素转换酶2 三氮脒 

分 类 号：R285[医药卫生—中药学]