玉屏风散加味方干预慢性阻塞性肺疾病气道重塑的探讨

Intervention Effect of Modified Yupinfeng San on COPD Airway Remodeling

目的:探究玉屏风散加味方对慢性阻塞性肺疾病(COPD)气道重塑病理形态的影响及其对相关细胞因子基质金属蛋白酶-9(MMP-9),金属蛋白酶组织抑制剂-1(TIMP-1)和转化生长因子-β1(TGF-β1)的影响。方法:SD大鼠48只,除正常组8只外,其余各组大鼠采用烟熏加脂多糖滴入叠加法复制COPD动物模型,造模成功的大鼠随机分为模型组,玉屏风散加味方高、中、低剂量组(30,10,5 g·kg-1),阳性药物组(罗红霉素胶囊),ig给药30 d后,取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,并用酶联免疫吸附测定(ELISA)法检测大鼠肺泡灌洗液(BALF)中的MMP-9,TIMP-1,TGF-β1的含量。结果:与正常组比较,模型组大鼠肺组织病理形态出现显著改变,支气管壁黏膜充血,水肿以肺泡巨噬细胞(AM),中性粒细胞(NEU),淋巴细胞(LYM),嗜酸性粒细胞(EOS)炎性细胞浸润较为明显,模型组MMP-9,TIMP-1,TGF-β1表达水平明显升高(P<0.05);与模型组比较,玉屏风散加味方组大鼠肺组织纤毛倒伏、粘连、缺失;上皮细胞坏死、脱落;支气管壁黏膜充血、水肿以及AM,NEU炎性细胞浸润程度均有所改善,其中高剂量组较为明显(P<0.05),玉屏风散加味方高、中剂量组下调细胞因子MMP-9,TIMP-1,TGF-β1表达水平明显(P<0.05)。结论:玉屏风散加味方可影响COPD气道重塑的病理形态,下调MMP-9,TIMP-1和TGF-β1的过度表达,可能为该方药干预COPD气道重塑作用机制之一,且以高剂量效果最为明显。

Objective： To explore the effect of modified Yupinfeng San（MYS） on the pathological morphology of chronic obstructive pulmonary disease（COPD） airway remodeling,and its regulatory effect on relevant cytokines matrix metalloproteinases-9（MMP-9）,tissue inhibitors metalloproteinases-1（TIMP-1） and transforming growth factor-β1（TGF-β1）. Method： Totally 60 SD rats were selected. Except for 10 rats in the normal group,all of the remaining rats were included in the COPD animal model by means of smoking and lipopolysaccharide dripping and overlaying method. After the successful modeling,the rats were randomly divided into the model group,MYS high,middle and low-dose groups,and the positive drug group（Roxithromycin capsules）. After the administration for 30 days,rat lung tissues were collected to prepare pathological slices. HE staining was used to observe histopathological changes in lung tissues,and ELISA method was adopted to detect MMP-9,TIMP-1 and TGF-β1in rat bronchalveolar lavage fluid（BALF）. Result： Compared with the normal group,the model group showed significant changes in lung tissue pathology morphology（P 〈0. 05）,with mucosal hyperemia and edema on bronchial walls,significant inflammatory cell infiltration in alveolar macrophages（AM）,neutrophil（NEU）,lymphocyte（LYM） and eosnophils（EOS）,and significant increases in MMP-9,TIMP-1and TGF-β1expression levels（P 〈0. 05）; compared with the model group,MYS groups showed lodging,adhesion and missing in lung cilia,epithelial cell necrosis and detachment,and alleviation in bronchial mucosal hyperemia and edema,and inflammatory cell infiltration in AM and NEU,which was evident in the high dose group（P〈 0. 05）. In MYS high and middle-dose groups,cytokines MMP-9,TIMP-1 and TGF-β1expression levels decreased significantly（P 〈0. 05）. Conclusion： MYS may affect the pathological changes of COPD airway remodeling,one of its action mechanisms in intervening COPD airway remodeling may be the down-regulation of excessive MMP-9,TIMP-1 and TGF-β1expressions,which is most obvious in the high-dose group.