复方红景参丸对慢性阻塞性肺炎模型大鼠肺功能的作用及其机制

Effects and mechanism of Compound Hongjingshen Pills on pulmonary function of rats with chronic obstructive pulmonary disease

目的研究复方红景参丸对慢性阻塞性肺炎(COPD)模型大鼠肺功能、炎性因子及p38丝裂原活化蛋白激酶(p38MAPK)通路的影响。方法SPF级60只SD大鼠,随机分为空白对照组、模型对照组、氨茶碱组及复方红景参丸低、中、高剂量组,通过烟熏和气道滴入脂多糖(LPS)建立慢性阻塞性肺炎模型。给药4周后,检测大鼠用力肺活量(FVC)、第0.1秒用力呼气容积(FEV0.1)和呼气峰流速(PEF),统计肺泡灌洗液白细胞数目及分类,苏木精-伊红(HE)染色观察肺组织病理变化,采用血清酶联免疫吸附法(ELISA)检测血清LTB4、IL-6、IL-1β、TNF-α的水平,Western blot检测肺组织TNF-α、p38MAPK、p-p38MAPK蛋白表达。结果与空白对照组比较,模型对照组大鼠FVC、FEV0.1、PEF水平均降低(P<0.01),肺泡灌洗液白细胞总数、巨噬细胞、淋巴细胞及中性粒细胞数均升高(P<0.01),血清LTB4、IL-6、IL-1、TNF-α水平均升高(P<0.01),肺组织中TNF-α、p-p38MAPK的蛋白表达升高(P<0.01);与模型对照组比较,氨茶碱组及复方红景参丸各剂量组各指标均呈现不同程度逆转(P<0.05,P<0.01)。HE染色发现,模型对照组支气管壁有大量炎性细胞浸润,腺体增生;氨茶碱组及复方红景参丸各剂量组支气管炎症及破坏程度有所减轻。结论复方红景参丸能明显改善慢性阻塞性肺炎模型大鼠的肺功能,其机制可能与抑制p38MAPK通路的磷酸化,下调炎性因子的水平有关。

AIM To observe the effects of Compound Hongjingshen Pills on pulmonary function,inflammatory cytokines and p38 MAPK pathway of rats with chronic obstructive pulmonary disease(COPD).METHODS Sixty SD rats of SPF grade were randomly divided into control group,model group,aminophylline group and groups for low dose,medium dose and high dose uses of Compound Hongjingshen Pills.Rat models of COPD were established by smoking and airway instillation of lipopolysaccharide(LPS).After four weeks of intragastric administration,rats were subjected to measurement of forced vital capacity(FVC),forced expiratory volume at 0.1 s(FEV0.1)and peak expiratory flow(PEF);counts and classification of white blood cells in bronchoalveolar lavage fluid;the observation of the pulmonary pathological changes by HE;the detection of serum levels of inflammatory cytokines,such as LTB4,IL-6,IL-1β,and TNF-αby ELISA;and the determination of the pulmonary protein expressions of TNF-α,p38 MAPK,p-p38 MAPK by Western blot.RESULTS Compared with the blank control group,the model group displayed decreased levels of FVC,FEV0.1 and PEF(P<0.01),increased total number of white blood cells,macrophages,lymphocytes and neutrophils in alveolar lavage fluid(P<0.01),and increased serum levels of LTB4,IL-6,IL-1 and TNF-α(P<0.01),increased pulmonary protein expressions of TNF-αand p-p38 MAPK(P<0.01).Compared with the model group,the aminophylline group and Compound Hongjingshen Pills groups shared differently reversed levels of all indexes(P<0.05,P<0.01).The large number of inflammatory cells infiltration and glandular hyperplasia in the bronchial wall of the model control group revealed by HE were reduced in the aminophylline group and Compound Hongjingshen Pills groups.CONCLUSION Compound Hongjingshen Pills can obviously improve the pulmonary function of COPD rat models,the mechanism may be related to inhibition of the phosphorylation of p38 MAPK pathway and down-regulation of the expression of inflammatory cytokines.