甜橙黄酮通过调节AMPK/mTOR信号通路改善呼吸道合胞病毒感染大鼠的肺组织损伤  

Sinensetin Improve Lung Tissue Damage in Rats Infected with Respiratory Syncytial Virus by Regulating AMPK/mTOR Signaling Pathway

作　　者：龙苏 袁媛 禹文峰 杨国辉 刘晓娴 LONG Su;YUAN Yuan;YU Wen-feng;YANG Guo-hui;LIU Xiao-xian(Department of Emergency,Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou,550002,China;Basic Medical College of Guizhou Medical University,Guiyang,Guizhou,550025,China;Internal Medicine ICU,Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou,550002,China)

机构地区：[1]贵州医科大学附属医院急诊科,贵州贵阳550002 [2]贵州医科大学基础医学院,贵州贵阳550025 [3]贵州医科大学附属医院内科ICU,贵州贵阳550002

出　　处：《现代生物医学进展》2023年第8期1424-1429,共6页Progress in Modern Biomedicine

基　　金：贵阳市科技计划项目([2020]-16-8号);贵州省卫生健康委科学技术基金项目(gzwjkj2020-1-024)。

摘　　要：目的:探讨甜橙黄酮通过AMP依赖的蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对呼吸道合胞病毒(RSV)感染大鼠肺组织损伤的改善作用。方法:将30只雄性Wistar大鼠分为对照组、模型组、甜橙黄酮低剂量组(14 mg/kg)、甜橙黄酮中剂量组(28 mg/kg)、甜橙黄酮高剂量组(56 mg/kg)、甜橙黄酮高剂量+AICAR组(56 mg/kg+500 mg/kg的AMPK激活剂AICAR),计算大鼠肺指数。实时荧光定量聚合酶链式反应(qRT-PCR)法测定肺组织RSV病毒载量,酶联免疫吸附(ELISA)法测定大鼠肺泡灌洗液炎症因子水平,HE染色测定肺组织病理,蛋白免疫印迹(Western blot)法测定AMPK/mTOR通路蛋白表达。结果:与对照组相比,模型组大鼠肺组织存在炎性浸润,排列松散,肺指数、肺组织RSV病毒载量、肺泡灌洗液白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平、炎症评分、p-AMPK/AMPK、mTORC1蛋白表达升高(P<0.05);与模型组相比,甜橙黄酮低剂量组、甜橙黄酮中剂量组、甜橙黄酮高剂量组大鼠肺组织损伤减轻,大鼠肺指数、肺组织RSV病毒载量、肺泡灌洗液IL-1β、IL-6、TNF-α水平、炎症评分、p-AMPK/AMPK、mTORC1蛋白表达降低(P<0.05);与甜橙黄酮高剂量组相比,甜橙黄酮高剂量+AICAR组大鼠肺组织损伤加重,肺指数、肺组织RSV病毒载量、肺泡灌洗液IL-1β、IL-6、TNF-α水平、炎症评分、p-AMPK/AMPK、MTORC1蛋白表达升高(P<0.05)。结论:甜橙黄酮可能通过抑制AMPK/mTOR信号通路发挥对RSV诱导的大鼠抗炎、抗病毒、抗肺部损伤作用。Objective:To investigate the ameliorating effect of Sinensetin on lung tissue damage in rats infected with respiratory syncytial virus(RSV)through AMP-dependent protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:30 male Wistar rats were grouped into control group,model group,low-dose Sinensetin group(14 mg/kg),medium-dose Sinensetin group(28 mg/kg),high-dose Sinensetin group(56 mg/kg),high-dose Sinensetin combined AICAR group(56 mg/kg combined 500 mg/kg of AMPK activator AICAR),the lung index of rats was calculated.The viral load of RSV in lung tissue was determined by quantitative real-time polymerase chain reaction(qRT-PCR).The levels of inflammatory factors in alveolar lavage fluid of rats were determined by enzyme-linked immunosorbent assay(ELISA).Lung histopathology was determined by HE staining,and Western blot was used to measure the expression of AMPK/mTOR pathway proteins.Results:Compared with the control group,the lung tissue of the model group had inflammatory infiltration,and was loosely arranged,the lung index,RSV viral load in lung tissue,levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid,inflammation score,expression of p-AMPK/AMPK and mTORC1 protein increased(P<0.05).Compared with the model group,the rats of the low-dose Sinensetin group,the medium-dose Sinensetin group,and the high-dose Sinensetin group had reduced lung tissue damage,the lung index of rats,RSV viral load in lung tissue,levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,inflammation score,expression of p-AMPK/AMPK,and mTORC1 decreased(P<0.05).Compared with the high-dose Sinensetin group,the lung tissue damage of the rats of the high-dose Sinensetin combined AICAR group was aggravated,the lung index,RSV viral load in lung tissue,levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,inflammation score,expression of p-AMPK/AMPK and MTORC1 increased(P<0.05).Conclusion:Sinensetin may play anti-inflammatory,anti-viral and anti-lung injury effec

关 键 词：甜橙黄酮 呼吸道合胞病毒 肺组织损伤 AMPK/mTOR信号通路 

分 类 号：R-33[医药卫生] R373.14