Li Yatan, Zhao Jun, Shao Hua, Jia Wei, Su Deqi, Liu Tao
Department of Toxicology, School of Public Health, Xinjiang Medical University, Urumqi, China.
Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang, Urumqi, China.
Ann Transl Med. 2022 Feb;10(4):222. doi: 10.21037/atm-22-331.
Chronic obstructive pulmonary disease (COPD) is diagnosed based on the clinical symptoms, risk factors, and pulmonary function tests. Exposure to cigarette smoke (CS), microbial infection stimulates monocytes and macrophages to rapidly synthesise and release inflammatory factors. A previous study of (TAF) revealed that it had significant anti-inflammatory and anti-oxidation effects on a pneumonia disease. Based on recent studies of the inflammatory pathway of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB), we will explore the influence of TAF on COPD.
Wistar rats were randomly divided into blank control group, Model Group, low-dose TAF + model group, middle-dose TAF + model group, high-dose TAF + model group, positive control + model group. Except for the blank control group, COPD inflammation models were established in all groups by CS poisoning and LPS. Prior to the daily poisoning, 125 mg/kg, 250 mg/kg, and 500 mg/kg of TAF were administered by gavage in the low-, middle-, and high-dose groups, respectively, and dexamethasone solution (1 mg/kg, once daily) was administered continuously in the positive control group on the last 5 days of modelling. General signs, lung function indices, lung imaging results, complete blood count, lung histopathological changes, inflammatory factors in the alveolar lavage fluid, relative expressions of TLR4, IκB kinase α (IKKα), p65, as well as IL-1β proteins and their mRNA relative expressions were measured and compared between each group.
Compared with the blank control group, TAF effectively reduced pulmonary parenchymal oedema (wet-to-dry ratio) and respiratory secretions. It also significantly delayed lung function injury. Lung X-ray imaging and haematoxylin and eosin staining. Blood routine examination results showed that TAF effectively inhibited the increase of white blood cell, lymphocyte, and eosinophil counts, decreased the release of inflammatory cytokines [IL-1β, IL-6, IL-8, TNF-α, and transforming growth factor-1β (TGF-1β)] and promoted the release of IL-10. It also inhibited the relative expressions of TLR4, IKKα, p65, IL-1β proteins, as well as IL-1 receptor-associated kinase (IRAK-1), IKKɑ, p65, and IL-1β mRNA.
Early intervention of TAF can reduce the occurrence of COPD, reduce the development of inflammation via TLR/NF-κB pathway, and provide reference for further study of the medicinal value of TAF.
慢性阻塞性肺疾病（COPD）依据临床症状、风险因素及肺功能测试进行诊断。接触香烟烟雾（CS）、微生物感染会刺激单核细胞和巨噬细胞快速合成并释放炎症因子。先前一项关于（TAF）的研究表明，它对肺炎疾病具有显著的抗炎和抗氧化作用。基于近期对Toll样受体4（TLR4）/核因子κB（NF-κB）炎症通路的研究，我们将探究TAF对COPD的影响。
将Wistar大鼠随机分为空白对照组、模型组、低剂量TAF+模型组、中剂量TAF+模型组、高剂量TAF+模型组、阳性对照+模型组。除空白对照组外，其余各组均通过CS中毒和脂多糖建立COPD炎症模型。在每日中毒前，低、中、高剂量组分别经口灌胃给予125mg/kg、250mg/kg和500mg/kg的TAF，阳性对照组在建模的最后5天连续给予地塞米松溶液（1mg/kg，每日1次）。测量并比较各组的一般体征、肺功能指标、肺部影像学结果、血常规、肺组织病理学变化、肺泡灌洗液中的炎症因子、TLR4、IκB激酶α（IKKα）、p65以及IL-1β蛋白的相对表达及其mRNA相对表达。
与空白对照组相比，TAF有效减轻了肺实质水肿（湿干比）和呼吸道分泌物。它还显著延缓了肺功能损伤。肺部X线成像及苏木精-伊红染色。血常规检查结果显示，TAF有效抑制了白细胞、淋巴细胞和嗜酸性粒细胞计数的增加，减少了炎症细胞因子[IL-1β、IL-6、IL-8、肿瘤坏死因子-α（TNF-α）和转化生长因子-1β（TGF-1β）]的释放，并促进了IL-10的释放。它还抑制了TLR4、IKKα、p65、IL-1β蛋白以及IL-1受体相关激酶（IRAK-1）、IKKɑ、p65和IL-1β mRNA的相对表达。
TAF的早期干预可降低COPD的发生，通过TLR/NF-κB途径减少炎症发展，为进一步研究TAF的药用价值提供参考。
