玉屏风散加味方对慢性阻塞性肺疾病大鼠气道炎症微环境的影响

Effect of Yupingfengsan improved decoction on airway inflammatory microenvironment in rats with COPD

目的探究玉屏风散加味方对慢性阻塞性肺疾病(COPD)大鼠气道炎症微环境相关因子分泌型免疫球蛋白A(SIgA)、多聚免疫球蛋白受体分泌片(SC)、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)的影响。方法将36只雄性Wistar大鼠随机分为正常组、模型组、罗红霉素组、玉屏风散加味方低剂量组、玉屏风散加味方中剂量组、玉屏风散加味方高剂量组,每组6只。除正常组外,其余组均采用气管内注入脂多糖(LPS)和持续被动烟熏刺激的方法复制大鼠COPD模型,模型成功后给予大鼠继续隔天烟熏刺激8周,于实验第17周开始各给药组给予相应剂量药物灌胃,模型组给予生理盐水灌胃,共灌胃28 d。末次灌胃24 h后,取各组大鼠肺组织做病理切片,苏木素-伊红(HE)染色观察肺组织病理学变化,并用酶联免疫吸附(ELISA)法检测大鼠肺组织匀浆中SIgA、SC,TNF-α、IL-8的表达水平。结果模型组大鼠气管上皮脱落、充血,可见肺大泡,肺内细支气管上皮增生、管腔变窄、管壁增厚,管壁及肺间质周围可见炎性细胞浸润;玉屏风散加味方各组大鼠肺内细支气管上皮增生不明显,管壁及肺间质周围炎性细胞浸润不明显,可见肺大泡,细支气管管腔狭窄及间质炎性细胞浸润等情况较模型组有明显改善,且高剂量组改善效果更明显。模型组大鼠肺组织匀浆中SIgA、IL-8、SC表达水平与正常组比较差异均无统计学意义(P均>0.05),TNF-α表达水平明显高于正常组(P<0.05)。玉屏风散加味方低剂量组SIgA表达水平和玉屏风散加味方中、低剂量组SC表达水平均明显高于模型组(P均<0.05),玉屏风散加味方高、低剂量组TNF-α表达水平明显低于模型组(P均<0.05);玉屏风散加味方高、中剂量组SIgA表达水平和玉屏风散加味方高剂量组SC表达水平、玉屏风散加味方中剂量组TNF-α表达水平、玉屏风散加味各剂量组IL-8表达水平与模型组比较差异均无统计学意义(P均>0.05)。结论玉屏风散加味方可改善COPD模型大鼠肺组织病理形态,增强SIgA和SC的表达,降低TNF-α和IL-8的表达,提示该方药可干预COPD气道炎症微环境,增强机体局部黏膜免疫功能,减轻炎症反应。

Objective It is to explore the effect of Yupingfengsan improved decoction on airway inflammatory microenvironment related factors such as secretory immunoglobulin A （SIgA） , polymeric immunoglobulin receptor secretory component （ SC）, tumor necrosis factor alpha （TNF-α） , interleukin-8 （ IL-8 ） in the rats with chronic obstructive pulmonary disease （COPD）. Methods 36 male Wistar rats were randomly divided into normal group, model group, Roxithromyein group, low dose Yupingfengsan improved decoction group, medium dose Yupingfengsan improved decoction group, high dose Yupingfengsan improved decoction group, each group had 6 rats. All the rats except in normal group were given lipopolysaecharide （LPS） by trachea injection and a continuous passive smoking to establish COPD models. After the models were successfully established, the rats were treated with continuous passive smoking every other day for 8 weeks. On the next week, every treatment group was treated with respective medicine by garage, the model group was given normal saline by garage. The treatments lasted for 28 days. In 24 hours after the last garage, the lung tissue of all the rats were gotten to make pathological section and stained by HE to observe the pathological changes of lung tissue, and to detect the expression levels of SIgA, SC, TNF-α and IL-8 by ELISA method. Results Obvious tracheal epithelial shedding, hyperemia, bullae, lung bronchiolar epithelial hyperplasia, luminal narrowing, wall thickening, wall and interstitial lung peripheral inflamma- tory cells infiltration were found in lung tissues of rats in model group, the lung bronchiolar epithelial hyperplasia was not obvious, the tube wall and the lung interstitial infiltration of inflammatory cells around was not obvious, bullae could be found in every Yupingfeng improved decoction treated group, and bronchial stenosis and interstitial infiltration of inflammatory ceils and other symptoms were obviously improved compared with the model group, the improvements in the high dose group were more obvious. Compared with the normal control group, the expression levels of SIgA and IL-8 in model group decreased, the SC expression level increased, the difference was not statistically significant （ P 〉 0. 05） ; the TNF-α expression level increased, the difference was statistically significant （ P 〈 0.05 ）. Compared with the model group, the SIgA expression level of low dose Yupingfeng improved decoction group increased, the SC expression level of low and middle dose Yupingfeng improved decoction group increased, the TNF-α expression level of low and high dose Yupingfeng improved decoction group decreased, the difference was statistically significant （ P 〈 0.05 ） ; the SIgA expression level of middle and high dose Yupingfeng improved decoction group increased, the SC expression level of Yupingfengsan flavored high dose group increased, the TNF-α expression level of middle dose Yupingfeng improved decoction group decreased, the IL- 8 expression level of low dose Yupingfeng improved decoction group decreased, the difference was not statistically significant （P 〉 0.05）. Conclusion Yupingfeng improved decoction can improve the pathological morphology of lung tissue of COPD rats, enhance the expression levels of SIgA and SC, reduce the high expression levels of TNF-α and IL-8, this suggesting that the prescription can regulate COPD airway inflammatory mieroenvironment, enhance the local mueosal immune and relieve inflammation reaction.