加味六安煎对咳嗽变异性哮喘豚鼠肺组织病理及辅助性T细胞1、2类细胞因子的影响

Effects of Modified Liu′an Decoction on Lung Histopathology and Th1/Th2 Cytokines in Guinea Pigs with Cough Variant Asthma

目的:观察加味六安煎对咳嗽变异性哮喘豚鼠肺组织病理及辅助性T细胞1、2类细胞因子水平的影响,探讨免疫相关作用机制。方法:将30只雄性豚鼠随机分为对照组、模型组、孟鲁司特钠组、中药低中高剂量组。除对照组外均腹腔注射卵蛋白及氢氧化铝致敏后用卵蛋白雾化激发,建立咳嗽变异性哮喘(CVA)模型,相应给药处理。观察肺组织病理形态变化,检测CVA豚鼠肺泡灌洗液中白细胞介素-12(IL-12)、白细胞介素-13(IL-3)。结果:光镜:CVA模型豚鼠较正常组支气管平滑肌增生肥厚,肺组织充血水肿,体积增大,周围炎症细胞浸润,杯状细胞及黏液栓增多,肺泡扩张、塌陷;观察组较模型组肺组织充血水肿、平滑肌增生肥厚及黏液栓等情况均不同程度减轻。透射电镜:模型组较正常组肺泡壁增厚、肺间质充血明显,Ⅱ型肺泡上皮绒毛脱落,线粒体数量减少,部分肿胀。观察组较模型组肺泡壁增厚、肺泡上皮绒毛脱落程度轻,胞质内线粒体数量多。肺泡灌洗液(BALF):模型组较正常组IL-12降低,IL-13升高,IL-12/IL-13下降但不显著;观察组较模型组IL-12均上升,其中中药中、高剂量组上升显著;IL-13降低但不显著,IL-12/IL-13均上升,中药中、高剂量组升高明显。结论:加味六安煎能减少CVA豚鼠炎症细胞浸润,减轻肺组织充血水肿及平滑肌增生肥厚,其作用机制可能与改善IL-12及IL-13水平,调控辅助性T细胞1、2免疫失衡有关。

Objective:To observe the effects of Modified Liu′an Decoction on lung histopathology and Th1/Th2 cytokine levels of guinea pigs with cough variant asthma(CVA),and to explore its immune-related mechanism.Methods:A total of 30 male guinea pigs were randomly divided into a normal control group,a CVA model group,a montelukast sodium group,and a modified Liuan Decoction low,medium and high dose groups.Ovalbumin and aluminum hydroxide was injected intraperitoneally for sensitization,and the CVA model was established by egg protein atomization stimulation.Each group was given corresponding administration treatment,with the exception of the normal control group.The pathological changes of lung tissue were observed,and the levels of interleukin 12(IL-12)and interleukin 13(IL-13)in the CVA guinea pigs′alveolar lavage fluid(BALF)were measured.Results:Observation under light microscopy:Compared with the normal group,the CVA model guinea pig presented with bronchial smooth muscle hyperplasia,lung tissue congestion and edema.There was also an increased volume,inflammatory cell infiltration in the surroundings,increase in goblet cells and mucus plugs,alveolar expansion and collapse.Compared with the CVA model group,the conditions of lung tissue congestion and edema,smooth muscle hyperplasia and mucus embolism in each drug intervention group were reduced to varying degrees.Observation under transmission electron microscope:Compared with the normal group,the alveolar wall of the CVA model group thickening and interstitial congestion were significant.In addition,there was a loss of typeⅡalveolar epithelial villi and a decrease in the number of mitochondria with and some swelling.The alveolar walls of each treatment group had varying degrees of thickening but not as severe as the model group.The loss of alveolar epithelial villi was lesser than that of the model group,and the number of mitochondria in the cytoplasm was greater than that of the model group.BALF:Compared with the normal group,IL-12 decreased,IL-13 increased and IL-12/IL-13 decreased but not significantly in the model group;Compared with the model group,IL-12 in the treatment group increased significantly,especially in the medium and high dose groups;IL-13 decreased but not significantly,IL-12/IL-13 increased,especially in medium and high dose groups.Conclusion:Modified Liu′an Decoction can reduce inflammatory cell infiltration in CVA guinea pigs,reduce lung congestion,edema,and smooth muscle hypertrophy.Its mechanism may be related to the improvement in IL-12 and IL-13 levels,as well as the regulation of Th1/Th2 immune imbalance.