基于miR-146/NF-κB信号通路探讨雷公藤多苷对肺纤维化大鼠的影响  

Effects of Tripterygium wilfordii polyglycosides on a rat model of pulmonary fibrosis via miR-146/NF-κB signaling pathway

作　　者：李泽峰 李传慧 周博文 马先 邵雨萌[1,2] 刘骅漫 贾新华[2] LI Ze-feng;LI Chuan-hui;ZHOU Bo-wen;MA Xian;SHAO Yu-meng;LIU Hua-man;JIA Xin-hua(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;The Hospital Affiliated to Shandong University of Traditional Chinese Medicine,Jinan 250000,China)

机构地区：[1]山东中医药大学,山东济南250355 [2]山东中医药大学附属医院,山东济南250000

出　　处：《中成药》2024年第10期3242-3248,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(81804034);青年岐黄学者培养工程(国中医药人教函[2022]256号);山东省自然科学基金项目(ZR2020MH353);山东省中医药高层次人才培育项目(鲁卫函[2023]143号);齐鲁卫生与健康领军人才培育工程(鲁卫人才字[2020]3号)。

摘　　要：目的探讨雷公藤多苷抑制大鼠肺纤维化进展的作用。方法随机选取6只大鼠作为空白组,34只大鼠气管穿刺注射硫酸博来霉素(5 mg/mL)构建肺纤维化模型。造模7 d后存活30只大鼠,随机分为模型组、醋酸泼尼松组(1.17 mg/kg)和雷公藤多苷低、中、高剂量组(1、3、6 mg/kg),给予相应剂量药物,连续21 d,给药期间观察大鼠一般表征。给药结束后,观察大鼠肺组织外观,比较肺系数,HE染色观察肺组织结构改变,Masson染色观察胶原沉积,采用肺组织纤维组织增生判断标准进行评分,ELISA法检测血清HYP、TNF-α、IL-1β、IL-6水平,RT-qPCR法检测肺组织miR-146a、NF-κB、Col-I mRNA表达,Western blot法检测肺组织p-P65、IRAK1、TRAF6、α-SMA蛋白表达。结果与空白组比较,模型组大鼠血清TNF-α、IL-6、IL-1β、HYP水平升高(P<0.01),肺组织miR-146a mRNA表达降低(P<0.01),NF-κB、Col-I mRNA及p-P65、IRAK1、TRAF6、α-SMA蛋白表达升高(P<0.01);与模型组比较,醋酸泼尼松组及雷公藤多苷各剂量组肺泡组织结构、炎性细胞浸润均有不同程度改善,纤维化程度均降低,肺组织miR-146a mRNA表达升高(P<0.01),血清TNF-α、IL-6、IL-1β、HYP水平、肺组织NF-κB、Col-I mRNA表达及p-P65、IRAK1、TRAF6、α-SMA蛋白表达降低(P<0.05,P<0.01),且雷公藤多苷的作用呈剂量依赖性。结论雷公藤多苷可延缓大鼠肺纤维化进展,其作用机制可能与调控miR-146/NF-κB信号通路有关。AIM To investigate the role of Tripterygium wilfordii polyglycosides as an inhibitor of pulmonary fibrosis progression in rats.METHODS In contrast to the six rats randomly selected into the blank group,another 34 rats were induced into a rat model of pulmonary fibrosis by bleomycin sulfate(5 mg/mL)injection using tracheal puncture followed by 7 days later random assignment of the survival thirty rats into the model group,the prednisone acetate group(1.17 mg/kg)and the low,medium and high dose tripterygium wilfordii polyglycosides groups(1,3,6 mg/kg)for 21 days corresponding dosing of the drugs.The general characteristics of rats were observed during administration.After the administration,the rats had their pulmonary morphology observed;their lung coefficients of each group compared;their structural changes of lung tissue observed using HE staining;their collagen deposition observed by Masson staining;and their hyperplastic conditions assessed by the criteria for judging pulmonary fibrous hyperplasia;their serum HYP,TNF-α,IL-1βand IL-6 levels detected by ELISA;their pulmonary expressions of miR-146a,NF-κB and Col-I mRNA detected by RT-qPCR method;and their pulmonary protein expressions of p-P65,IRAK1,TRAF6 andα-SMA detected by Western blot.RESULTS Compared with the blank group,the model group displayed increased levels of serum TNF-α,IL-6,IL-1βand HYP(P<0.01);decreased pulmonary miR-146a mRNA expression(P<0.01);and increased expressions of NF-κB,Col-I mRNA and p-P65,IRAK1,TRAF6 andα-SMA protein(P<0.01).Compared with the model group,the groups intervened with either prednisone acetate or Tripterygium wilfordii polyglycoside shared differently improved alveolar structure and inflammatory cell infiltration;reduced fibrosis;increased pulmonary miR-146a mRNA expression(P<0.01);increased levels of TRAF6-α,IL-6,IL-1βand HYP in serum,and expressions of NF-κB and Col-I mRNA and expression of p-P65,IRAK1,TRAF6 andα-SMA protein of the lung tissue(P<0.05,P<0.01)as well.CONCLUSION Tripterygium wilfordii polyglycos

关 键 词：雷公藤多苷 肺纤维化 miR-146/NF-κB信号通路 炎症因子 ECM沉积 

分 类 号：R285.5[医药卫生—中药学]