腺苷A2a受体在系统性硬化症相关间质性肺病中的作用及机制研究  

Role and mechanism of adenosine A2a receptor in systemic sclerosis associated interstitial lung disease

作　　者：戴才俊 董一枝 严丹 涂军伟 DAI Caijun;DONG Yizhi;YAN Dan;TU Junwei(Department of Pulmonary and Critical Care Medicine,Affiliated Jinhua Hospital,Zhejiang University School of Medicine,Jinhua Municipal Central Hospital,Jinhua 321000,Zhejiang,China)

机构地区：[1]浙江大学医学院附属金华医院,金华市中心医院呼吸与危重症医学科,浙江金华3210001

出　　处：《中国现代医生》2023年第36期13-17,共5页China Modern Doctor

基　　金：浙江省金华市公益性技术应用研究项目(2022-4-123)。

摘　　要：目的研究腺苷A2a受体(A2a receptor,A2aR)的激活对小鼠系统性硬化症相关间质性肺病(systemic sclerosis associated interstitial lung disease,SSc-ILD)的保护作用及机制。方法选取24只野生型雌性Balb/c小鼠,随机分为三组:正常对照组(wild normal control group,WN组)、造模组(wild model group,WM组)、造模+A2aR激动剂(CGS21680)组(WM with CGS21680 group,WMC组)。建模结束2周后,取小鼠的肺组织和血清。对肺组织进行苏木精-伊红染色、马松染色及羟脯氨酸含量测定,观察炎症浸润及纤维化程度。酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测小鼠的血清及肺组织晚期氧化蛋白产物、肺组织还原型谷胱甘肽,测定血清及肺组织的氧化应激水平。结果(1)苏木精-伊红染色和马松染色下,WM组小鼠肺部呈现炎症浸润及纤维化,WMC组小鼠较WM组小鼠减轻;(2)WM组小鼠肺组织的羟脯氨酸含量、血清及肺组织晚期氧化蛋白产物含量均较WN组小鼠升高(P<0.01),WMC组小鼠较WM组小鼠降低(P<0.01);(3)WM组小鼠的肺组织还原型谷胱甘肽含量较WN组小鼠降低(P<0.01),WMC组小鼠较WM组小鼠升高(P<0.05)。结论A2a R激活可通过抗氧化作用机制减轻SSc-ILD的炎症和纤维化程度。Objective To study the protective effect and mechanism of adenosine A2a receptor(A2aR)activation in the pathogenesis of systemic sclerosis associated interstitial lung disease(SSc-ILD).Methods A total of 24 healthy female Balb/c mice were randomly divided into three groups:wild normal control(WN)group,wild model(WM)group,WM with CGS21680(WMC)group.Two weeks after the end of injections,the lung samples and serum of mice were collected.A part of lung tissues were obtained for hematoxylin eosinstaining,Masson staining and determination of hydroxyprolineto observe the degree of inflammation and fibrosis.Enzyme linked immunosorbent assay(ELISA)was used to detect advanced oxidative protein products in mouse serum and lung tissue,reduced glutathione in lung tissue,and oxidative stress levels in serum and lung tissue.Results①Underhematoxylin eosinstaining and Masson staining,the lungs of mice in WM group showed inflammation infiltration and fibrosis,while mice in WMC group showed a reduction compared to mice in WM group;②The content of hydroxyproline in lung tissue,serum and late stage oxidative protein products in lung tissue of WM group mice increased compared to WN group mice(P<0.01),while the content of WMC group mice decreased compared to WM group mice(P<0.01);③The reduced glutathione content in lung tissue of WM group mice was lower than that of WN group mice(P<0.01),while WMC group mice were higher than WM group mice(P<0.05).Conclusion The activation of A2aR ameliorated the degree of inflammation and fibrosis in SSc-ILD,possibly through the antioxidant mechanism.

关 键 词：硬皮病相关间质性肺病 腺苷A2A受体 晚期氧化蛋白产物 还原型谷胱甘肽 

分 类 号：R332[医药卫生—人体生理学]