DDAH1通过抑制氧化应激及炎症反应缓解PM2.5诱导的肺损伤机制研究  

DDAH1 alleviates PM2.5-induced lung injury by inhibiting oxidative stress and inflammatory response

作　　者：汤兰兰 王真 钱娇 沈剑 TANG Lan-lan;WANG Zhen;QIAN Jiao(Department of Respiratory and Critical Care Medicine,Chengdu Third People's Hospital/Affiliated Hospital of Southwest Jiaotong University,Chengdu Sichuan 610031,China)

机构地区：[1]成都市第三人民医院/西南交通大学附属医院呼吸与危重症医学科,四川成都610031

出　　处：《临床和实验医学杂志》2023年第21期2245-2249,共5页Journal of Clinical and Experimental Medicine

基　　金：四川省医学会科研课题(编号:q20009)。

摘　　要：目的探讨二甲基精氨酸二甲胺水解酶1(DDAH1)通过抑制氧化应激及炎症反应缓解PM2.5诱导的小鼠肺损伤的保护作用。方法32只雌性C57BL/6野生型小鼠,按照随机数字表法将其分为4组,分别为对照组、模型组、DDAH1高剂量组、DDAH1低剂量组,每组各8只。除对照组滴注0.9%氯化钠溶液外,其余各组室温下用无菌0.9%氯化钠溶液将PM2.5稀释至终浓度220μg/100μL,小鼠气管滴注PM2.5溶液60μL,每天1次,连续暴露7 d。其中,DDAH1高剂量组气管滴注PM2.5溶液前30 min,给予300 ng重组人DDAH1蛋白进行滴鼻处理。DDAH1低剂量组气管滴注PM2.5溶液前30 min,给予100 ng重组人DDAH1蛋白进行滴鼻处理。检测小鼠支气管灌洗液中炎症因子[白细胞介素(IL)-6、IL-8、IL-1β、肿瘤坏死因子-α(TNF-α)]及肺组织中丙二醛、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)含量;观察各实验组小鼠肺组织的病理学改变,肺组织中的细胞黏附分子-1(ICAM-1)、血管细胞黏附因子1(VCAM-1)、不对称二甲基精氨酸(ADMA)、转化生长因子-β(TGF-β)、诱导型一氧化氮合酶(iNOS)蛋白表达。结果与对照组相比,模型组肺泡灌洗液中IL-6、IL-8、TNF-α及IL-1β水平均明显升高,差异均有统计学意义(P<0.05);与模型组相比,DDAH1高剂量组、DDAH1低剂量组肺泡灌洗液中IL-6、IL-8、TNF-α及IL-1β水平均明显降低,差异均有统计学意义(P<0.05)。与对照组相比,模型组肺组织中丙二醛水平明显升高,SOD及CAT水平均明显降低,差异均有统计学意义(P<0.05);与模型组相比,DDAH1高剂量组、DDAH1低剂量组肺组织中丙二醛水平明显降低,SOD及CAT水平均明显升高,差异均有统计学意义(P<0.05)。与对照组相比,模型组肺组织中ICAM-1、VCAM-1、TGF-β、iNOS、ADMA蛋白表达水平均明显升高,差异均有统计学意义(P<0.05);与模型组相比,DDAH1高剂量组、DDAH1低剂量组肺组织中ICAM-1、VCAM-1、TGF-β、iNOS、ADMA蛋白表达水平�Objective To investigate the protective effect of dimethylarginine dimethylamine hydrolase 1(DDAH1)on PM2.5-induced lung injury in mice by inhibiting oxidative stress and inflammatory response.Methods Thirty-two female C57BL/6 wild type mice were divided into control group,model group,high-dose DDAH1 group and low-dose DDAH1 group according to the random number table,with 8 mice in each group.Except for the control group,PM2.5 was diluted to a final concentration of 220μg/100μL with sterile normal saline at room temperature,and 60μL PM2.5 solution was instilled into the trachea once a day for 7 consecutive days.In the DDAH1 high dose group,300 ng recombinant human DDAH1 protein was intranasal instilled 30 minutes before intratracheally instilled PM2.5 solution.The low-dose DDAH1 group was given 100 ng recombinant human DDAH1 protein intranasal 30 minutes before intratracheally instilled PM2.5 solution.The contents of inflammatory factors[interleukin(IL)-6,IL-8,IL-1β,tumor necrosis factor-α(TNF-α)]in bronchial lavage fluid and malondialdehyde,superoxide dismutase(SOD),catalase(CAT)in lung tissue were detected.The pathological changes of lung tissue in each experimental group were observed,and the protein expressions of cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),asymmetric dimethylarginine(ADMA),transforming growth factor-β(TGF-β)and inducible nitric oxide synthase(iNOS)in lung tissue were observed.Results Compared with the control group,the levels of IL-6,IL-8,TNF-αand IL-1βin the alveolar lavage fluid of the model group were significantly increased,the differences were statistically significant(P<0.05);compared with the model group,the levels of IL-6,IL-8,TNF-αand IL-1βin the alveolar lavage fluid of the DDAH1 high-dose group and DDAH1 low-dose group were significantly decreased,the differences were statistically significant(P<0.05).Compared with the control group,the level of malondialdehyde in the lung tissue was significantly increased,and the levels of SOD and CAT w

关 键 词：小鼠 PM2.5 肺损伤 氧化应激 炎症反应 二甲基精氨酸二甲胺水解酶1 

分 类 号：R563[医药卫生—呼吸系统]