清金化痰汤通过p38MAPK/NF-κB信号通路改善大鼠急性气道炎症的作用和机制

Effect and Mechanism of Qingjin Huatan Tang in Improving Acute Airway Inflammation of Rats Through Signaling Pathways of p38MAPK/NF-κB

摘要:

目的：探讨清金化痰汤治疗急性气道炎症模型大鼠气道炎症性损伤和黏液高分泌的作用和机制。方法：脂多糖（LPS）诱导建立急性气道炎症大鼠模型，随机分为空白组、模型组、地塞米松组、清金化痰汤高、中、低剂量（7.44，3.72，1.86 g·kg^-1）组，各组大鼠自给药开始计时，第4，7天分批次处死。采集肺泡灌洗液（BALF），气管及肺组织，观察各组大鼠BALF中白细胞及细胞分类计数；酶联免疫吸附法（ELISA）检测BALF中白细胞介素（IL）-1β，IL-8，肿瘤坏死因子（TNF）-α以及黏蛋白（MUC5AC）；光镜下观察气管和肺组织病理学改变；蛋白免疫印迹法（Western blot）测定肺组织p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，p38MAPK），核转录因子-κB（NF-κB）抑制蛋白（IκBα），NF-κB p65蛋白表达水平。结果：清金化痰汤能抑制BALF中白细胞总数、中性粒细胞、淋巴细胞升高，减轻气管和肺组织的病理学炎症积分，减少细胞因子IL-1β，IL-8，TNF-α水平及黏蛋白MUC5AC的表达，下调肺组织p38MAPK，NF-κB p65蛋白表达，增加IκBα蛋白表达水平。结论：清金化痰汤具有抑制炎症细胞浸润，减少细胞因子和黏蛋白MUC5AC的表达，抑制气道炎症反应的作用；清金化痰汤通过调控肺组织p38MAPK/NF-κB信号通路，抑制气道黏蛋白分泌和细胞因子的释放，从而改善气道黏液高分泌状态及其炎症性损伤。

Abstract:

Objective: To investigate the effect and mechanism of Qingjin Huatan Tang in treatment of airway injury and mucus hypersecretion in acute airway inflammation model of rats. Method: The model of acute airway inflammation in rats was induced by lipopolysaccharide (LPS), and randomly divided into 6 groups, namely blank group, model group, Dexamethasone group, high-dose, medium-dose and low-dose Qingjin Huatan Tang (7.44, 3.72, 1.86 g·kg^-1) groups. Each group of rats was put to death in batches on the 4^th day and 7^th day after administration. Bronchoalveolar lavage fluid (BALF), trachea and lung tissues were collected to count the number of white blood cells and other types of cells in BALF of each group of rats. Cell factor of interleukin(IL)-1β, IL-8, tumor necrosis factor(TNF)-α and MUC5AC in BALF were detected with enzyme-linked immunosorbent assay (ELISA). Pathological changes of trachea and lung tissues were observed under light microscope. p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-kappa B (NF-κB) inhibition protein(IκBα), and NF-κB p65 in lung tissues were determined with Western blot. Result: Qingjin Huatan Tang can inhibit the increasing number of leukocyte, neutrophil, and lymphocyte in BALF, relieve pathological inflammation scores of trachea and lung tissues, reduce the level of cell factors IL-1β, IL-8, TNF-α and the expression of mucin MUC5AC, down-regulate the expressions of p38MAPK and NF-κB p65, and up-regulate the expression of IκBα in lung tissues. Conclusion: Qingjin Huatan Tang has effects in inhibiting infiltration of inflammatory cells and airway inflammatory response, reducing the expressions of cells and mucin MUC5AC, inhibiting inflammatory reaction of airway. Qingjin Huatan Tang can inhibit mucin secretion and release of cytokines by regulating signaling pathways of p38MAPK/NF-κB in lung tissues, so as to improve the state of mucus hypersecretion and inflammatory injury in airway.