基于TLR4/NF-κB信号通路探讨芪白平肺胶囊对慢性阻塞性肺疾病不同阶段大鼠肺血管重构的改善作用  

Exploration of Pulmonary Vascular Remodeling Improvement in Rats at Different Stages of Chronic Obstructive Pulmonary Disease by Qibai Pingfei Capsules Based on TLR4/NF-κB Signaling Pathway

作　　者：张璐 方莉[2] 徐淑钰 梁雪 朱洁[1] 童祥丽 李泽庚[2,3] ZHANG Lu;FANG Li;XU Shuyu;LIANG Xue;ZHU Jie;TONG Xiangli;LI Zegeng(Anhui University of Chinese Medicine,Hefei 230038,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;Anhui Provincial Key Laboratory of Application and Transformation of Traditional Chinese Medicine in Prevention and Treatment of Major Pulmonary Diseases,Hefei 230031,China)

机构地区：[1]安徽中医药大学,合肥230038 [2]安徽中医药大学第一附属医院,合肥230031 [3]中医药防治肺系重大疾病应用转化安徽省重点实验室,合肥230031

出　　处：《中国实验方剂学杂志》2025年第9期48-56,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金青年基金项目(82104780,82205074);安徽高校杰出青年项目(2022AH020044);安徽高校协同创新项目(GXXT-2021-084)。

摘　　要：目的:探讨芪白平肺胶囊对慢性阻塞性肺疾病(COPD)不同阶段大鼠肺血管重构的改善作用,分析其可能的作用机制。方法:将雄性SD大鼠随机分为正常组、早期COPD模型组、晚期COPD模型组、早期干预高剂量组、晚期干预高剂量组、早期干预低剂量组、晚期干预低剂量组、早期干预吡咯烷二硫代氨基甲酸盐(PDTC)组、晚期干预PDTC组,每组15只。采用香烟烟雾联合脂多糖(LPS)气道滴注的方法构建早期COPD大鼠模型,LPS气道内滴入、香烟烟雾联合低氧的方法构建晚期COPD大鼠模型。除正常组外,其余各组在实验第1天和第14天给予LPS气道滴入,每天烟熏1 h,并在第15天起开始给药,每天1次,连续40周。芪白平肺胶囊高、低剂量组分别给予芪白平肺胶囊1 g·kg^(-1)、250 mg·kg^(-1)大鼠灌胃,PDTC腹腔注射100 mg·kg^(-1)。晚期COPD模型组在第5~6周进行每天6 h的低氧。检测大鼠肺功能、平均肺动脉压力,苏木素-伊红(HE)染色法观察肺组织形态变化,马松(Masson)染色观察肺动脉的胶原沉积情况,酶联免疫吸附测定法(ELISA)检测肺组织中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)炎症因子水平;吉姆萨(Giemsa)染色检测各组大鼠肺泡灌洗液中的炎性细胞数量;蛋白免疫印迹法(Western blot)检测大鼠肺组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子-κB(NF-κB)、TNF-α、管内皮钙黏蛋白(VE-cadherin)、α-平滑肌肌动蛋白(α-SMA)、血小板内皮细胞黏附分子(CD31)蛋白表达。结果:与正常组比较,模型组大鼠肺功能中第0.3秒用力呼气容积(FEV_(0.3))、用力肺活量(FVC)及FEV_(0.3)/FVC均明显下降(P<0.05),肺血管增厚,肺部胶原沉积增多,平均肺动脉压及IL-6、IL-1β、TNF-α表达水平明显升高(P<0.05),巨噬细胞、淋巴细胞、中性粒细胞数量增多(P<0.05),TLR4、MyD88、NF-κB、TNF-α、α-SMA蛋白表达明显升高(P<0.05),VE-cadherin、CD31的蛋白�Objective:To investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease(COPD)and to analyze its possible mechanism of action.Methods:Male Sprague-Dawley(SD)rats were randomly divided into a normal group,an early COPD model group,an advanced COPD model group,an early-intervention high-dose group,a late-intervention high-dose group,an early-intervention low-dose group,a late-intervention low-dose group,an early-intervention pyrrolidine dithiocarbamate(PDTC)group,and a lateintervention PDTC group,with 15 rats in each group.A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide(LPS),and a rat model of advanced COPD was constructed by using airway infusion with LPS,cigarette smoke,and hypoxia.All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment,smoked for 1 h per day,and administered the drug once a day for 40 weeks from day 15 onward.In the high-and low-dose groups,rats were given 1 g·kg^(-1)and 250 mg·kg^(-1)Qibai Pingfei capsules,respectively by gavage,and in PDTC groups,rats were given 100 mg·kg^(-1)of PDTC by intraperitoneal injection.The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6.Lung function and mean pulmonary artery pressure were tested in rats.Morphologic changes in lung tissues were detected by hematoxylin-eosin(HE)staining.Collagen deposition in lung tissues was examined by Masson staining,and the levels of inflammatory factors including interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in lung tissues were detected by enzyme-linked immunosorbent assay(ELISA).The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining,and the protein expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB),TNF-α,vascular endothelial-cadherin(V

关 键 词：芪白平肺胶囊 慢性阻塞性肺疾病(COPD) 肺血管重构 内皮间质转化 Toll样受体4/核转录因子-κB(TLR4/NF-κB)信号通路 

分 类 号：R285[医药卫生—中药学] R259[医药卫生—中医学] R289