化纤散结复方颗粒通过PI3K/AKT/NF-κB信号通路改善大鼠矽肺纤维化  

Huaxian Sanjie compound granule improves silicosis fibrosis in rats through PI3K/Akt/NF-κB signaling pathway

作　　者：尹琴 杨洁 范存愈 梅凤 於薇 李娟 易莉萍 余贻汉 凌瑞杰 YIN Qin;YANG Jie;FAN Cun-yu;MEI Feng;YU Wei;LI Juan;YI Li-ping;YU Yi-han;LING Rui-jie(Department of Respiratory and Critical Care Medicine,Integrated Chinese and Western Medicine,Wuhan,Hubei 430015,China;不详)

机构地区：[1]湖北省中西医结合医院呼吸与危重症医学科,湖北武汉430015 [2]湖北中医药大学第一临床学院,湖北武汉430065 [3]华中科技大学同济医学院动物实验中心,湖北武汉430030 [4]湖北省中西医结合医院职业病科,湖北武汉430015

出　　处：《中国职业医学》2022年第3期272-279,共8页China Occupational Medicine

基　　金：湖北省自然科学基金面上项目(2020CFB560);武汉市中青年医学骨干人才项目(武卫通【2020】55号);湖北省公共卫生青年拔尖人才项目(鄂卫通【2021】74号)。

摘　　要：目的研究化纤散结复方颗粒改善大鼠矽肺纤维化的作用及其机制。方法将无特定病原体级雄性SD大鼠随机分为对照组、矽肺模型组和干预组,每组6只。采用一次性呼吸机联合非暴露式气管内滴注法,矽肺模型组和干预组大鼠均予1.0 mL质量浓度为50.0 g/L的二氧化硅悬浊液建立染矽尘大鼠模型,对照组大鼠予等体积0.9%氯化钠溶液。染尘24 h后,干预组大鼠予剂量为10 mL/kg体质量的化纤散结复方颗粒混悬液(质量浓度为212.5 g/L)灌胃,对照组和矽肺模型组大鼠均予等体积0.9%氯化钠溶液灌胃,每日1次。分别于染尘后第14和28天处死各组大鼠3只,进行肺组织病理学检查;以酶联免疫吸附实验检测大鼠血清和肺组织中白细胞介素-6(IL-6)、转化生长因子-β1(TGF-β1)水平,以蛋白质印迹法检查肺组织中磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)、核转录因子-κB(NF-κB)和Ⅰ型胶原(COLⅠ)蛋白相对表达水平。结果肺组织病理学检查结果显示,与同时间点矽肺模型组比较,干预组大鼠肺组织炎症反应、纤维结节、胶原纤维均明显减少,纤维化明显减轻。矽肺模型组大鼠第14和28天血清中IL-6和肺组织中IL-6、TGF-β1的水平均高于同时间点对照组(P值均<0.05),且第28天的上述指标均高于第14天(P值均<0.05)。矽肺模型组大鼠血清中TGF-β1水平和肺组织中PI3K、AKT、NF-κB、COLⅠ蛋白相对表达水平均高于对照组(P值均<0.05)。干预组大鼠第14和28天血清中IL-6和肺组织中IL-6、TGF-β1的水平均低于同时间点矽肺模型组(P值均<0.05);且干预组大鼠血清中TGF-β1水平和肺组织中PI3K、AKT、NF-κB、COLⅠ蛋白相对表达水平均高于对照组(P值均<0.05)。结论化纤散结复方颗粒可通过PI3K/AKT/NF-κB信号通路延缓和拮抗矽肺大鼠肺纤维化。ObjectiveTo study the effect and mechanism of Huaxian Sanjie compound granule on silicosis fibrosis in rats.MethodsThe specific pathogen free male SD rats were randomly divided into control group,silicosis model group and intervention group,with six rats in each group.Disposable ventilator combined with non-exposed intratracheal drip was used,the rats in the silicosis model group and intervention group were treated with 1.0 m L silica suspension with a mass concentration of50.0 g/L to establish silicon dust rat model,while the rats in the control group were treated with equal volume of 0.9%sodium chloride solution.After 24 hours of dust exposure,the rats in the intervention group were given 10 m L/kg body weight of Huaxian Sanjie compound granule suspension with a mass concentration of 212.5 g/L by gavage,while the rats in the control group and silicosis model group were given the same amount of 0.9%sodium chloride solution,once a day.Three rats in each group were sacrificed on the 14th and 28th day,respectively,and their lung tissues were separated for pathological examination.The levels of interleukin-6(IL-6)and transforming growth factor-β(TGF-β)in serum and lung tissues of rats were detected by enzyme-linked immunosorbent assay.The relative expression of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),nuclear factor-κB(NF-κB)and collagen typeⅠ(COLⅠ)in lung tissues was examined by Western blotting.ResultsThe result of lung histopathological examination showed that the inflammatory reaction,fibrous nodules and collagen fibers in the lung tissues of the intervention group were significantly reduced,and the fibrosis was significantly alleviated,when compared with the silicosis model group at the same time point.The levels of IL-6 in serum and IL-6 and TGF-β1 in lung tissue of silicosis model group at 14 and 28 days were higher than those of control group at the same time point(all P<0.05),and the above indexes on the 28th day were higher than those on the 14th day(all P<0.05).The levels of TGF-

关 键 词：化纤散结复方颗粒 矽肺 肺纤维化 白细胞介素-6 转化生长因子-Β PI3K/AKT/NF-κB 信号通路 Ⅰ型胶原 大鼠 

分 类 号：R135.2[医药卫生—劳动卫生] R114[医药卫生—公共卫生与预防医学]