摘要
目的:探讨烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶(NOX)抑制剂罗布麻宁对二氧化硅(SiO_(2))诱导的大鼠矽肺模型的干预作用,并探讨其作用机制。方法:于2021年10月,将24只SPF级SD雄性大鼠按随机数字表法分为对照组、矽肺模型组、罗布麻宁干预组,每组8只。采用一次性气管滴注SiO_(2)的方法染尘,罗布麻宁干预组大鼠于处理后第2天开始腹腔注射罗布麻宁50 mg/kg,3次/周。于28 d后处死大鼠,取肺组织称重后计算肺系数,苏木精-伊红染色和Masson染色分别观察各组大鼠肺组织病理学变化。检测肺组织NOX、活性氧(ROS)、谷胱甘肽过氧化物酶(GSH-Px)活力及丙二醛(MDA)水平;酶联免疫吸附试验法测定肺组织白细胞介素1β(IL-1β)、白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)表达;碱水解法检测羟脯氨酸(HYP)水平;蛋白免疫印迹法检测肺组织转化生长因子β1(TGF-β1)、E-钙黏蛋白(E-cad)及α-平滑肌蛋白(α-SMA)的表达。结果:与对照组相比,矽肺模型组大鼠体重降低,肺组织出现明显的炎性浸润及纤维化,肺系数、IL-1β、IL-6、TNF-α及TGF-β1水平均明显升高(P<0.05);与矽肺模型组比较,罗布麻宁干预组大鼠肺组织损伤明显改善,肺系数、NOX、ROS、MDA、IL-1β、IL-6、TNF-α及TGF-β1水平均降低,GSH-Px活力增加(P<0.05);与矽肺模型组比较,罗布麻宁干预组大鼠肺组织HYP和α-SMA表达均降低,E-cad水平增加(P<0.05)。结论:罗布麻宁可能通过减少矽肺大鼠氧化应激、炎性因子释放及抑制上皮-间质转化,缓解SiO_(2)诱导的大鼠纤维化作用。
Objective To investigate the intervention effect and its mechanism of apocynin,an inhibitor of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)on silicosis induced by silica(SiO_(2))in rats.Methods In October 2021,24 SPF SD male rats were divided into control group,silicosis model group and apocynin intervention group according to random number table method,with 8 rats in each group.SiO_(2) was exposed by one-time intratracheal instillation.The rats in the apocynin intervention group were intraperitoneally injected with apocynin 50 mg/kg,3 times a week,on the second day after treatment.The rats were sacrificed 28 days later,and lung coefficients were calculated after lung tissues were weighed.Hematoxylin-eosin staining and Masson staining were used to observe the lung histopathological changes in each group,respectively.The levels of NOX,reactive oxygen species(ROS),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in lung tissue were detected.The expressions of interleukin-1 beta(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)were determined by Enzyme-Linked Immunosorbent Assay(ELISA).The level of hydroxyproline(HYP)was detected by alkaline hydrolysate.The expressions of transforming growth factor beta 1(TGF-β1),E-cadherin(E-cad)andα-smooth muscle actin(α-SMA)in lung tissue were detected by Western blotting.Results Compared with the control group,the body weight of silicosis model group was decreased,the lung tissue showed obvious inflammatory infiltration and fibrosis,and the levels of lung coefficient,IL-1β,IL-6,TNF-αand TGF-β1 were significantly increased(P<0.05).Compared with the silicosis model group,the lung tissue injury in the apocynin intervention group was significantly improved,the lung coefficient,NOX,ROS,MDA,IL-1β,IL-6,TNF-αand TGF-β1 levels were decreased,and the activity of GSH-Px was increased(P<0.05).Compared with the silicosis model group,the expressions of HYP andα-SMA were decreased and the level of E-cad was increased in the apocynin interventio
作者
刘芳
贾强
厉铭
宋招远
胡晨阳
薄存香
Liu Fang;Jia Qiang;Li Ming;Song Zhaoyuan;Hu Chenyang;Bo Cunxiang(Department of Toxicology,Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University(Shandong Academy of Medical Sciences),Jinan 250062,China)
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2023年第10期801-807,共7页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
山东省自然科学基金(ZR2022MH293)
山东省医药卫生科技发展计划(202012040412)
山东省中医药科技发展计划(2021M153)
山东济南市科技局临床医学科技创新计划(202019109)。
关键词
矽肺
纤维化
罗布麻宁
上皮-间质转化
大鼠
NADPH氧化酶
活性氧
Silicosis
Fibrosis
Apocynin
Epithelial-mesenchymal transition
Rats
Nicotinamide adenine dinucleotide phosphate oxidase,NOX
Reactive oxygen species
