ABSTRACT
ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage （固本防哮饮） for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group， model group， low-， medium-， and high-dose of Guben Fangxiao Beverage group and montelukast sodium group， with 6 mice in each group. Except for the normal group， ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding， the low-， medium-， and high-dose groups of Guben Fangxiao Beverage were respectively given 12， 24， and 36 g/（kg·d）， the montelukast sodium group was given montelukast sodium granule 2.6 mg/（kg·d）， and the mice in the normal group and model group were given 20 ml of double-distilled water， all by gavage， once a day for 28 days. The levels of interleukin 4 （IL-4） and interleukin 5 （IL-5） in the lung tissue of mice were detected； HE staining was used to observe the pathology of the lung tissue and to score the inflammation； DHE staining was used to observe the level of reactive oxygen species （ROS） in the lung tissue， and the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ in the lung tissue were detected； the levels of serum superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA） and adenosine triphosphate （ATP） were detected； the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， haem oxygenase 1 （HO-1） and cAMP responsive element binding protein （CREB） in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group， the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score； DHE staining showed an increase in the level of ROS， and an increase in the levels of IL-4 and IL-5 in the lung tissues； the levels of serum SOD， CAT， and ATP were reduced， and the level of MDA was elevated； the activities of the mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ of the lung tissues were reduced， and the activities of p-AMPK， Nrf2， CREB protein expression decreased （P＜0.05）. Compared with the model group， the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced； the levels of ROS， IL-4 and IL-5 in the lung tissue were reduced； the levels of CAT and ATP in the serum increased， and the content of MDA was reduced； and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ， as well as the expression of CREB protein， were elevated in the lung tissue （P＜0.05）. Compared with the high-dose group， the MDA level of the medium-dose Guben Fangxiao Beverage group decreased （P＜0.05）. The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group， and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group （P＜0.05）. ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission， and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.