Leukotriene Receptor Antagonists Combined With Glycyrrhetinic Acid In The Airway Remodeling Of Bronchial Asthmatic Guinea Pigs

Objective To investigate the effects of leukotriene receptor antagonist montelukast sodium（MK）and/or glycyrrhetinic acid（GA）on the airway remodeling of bronchial asthma（asthma）and the expression of transforming growth factor-β₁（TGF-β₁）,Smad₇ Horizontal changes and their correlations.Method The SPF male Hartley guinea pigs were randomly divided into normal control group（group A）,asthma group（group B）,MK group（group B-1）,GA group（group B-2）and MK+GA group（group B-3）.All groups except group A were injected with ovalbumin（OVA）intraperitoneally and 1%OVA was inhaled to prepare asthma model of airway remodeling.Group A was replaced by saline solution.Group B-1 was given MK suspension intragastrically;Group B-2 was given GA suspension gavage;Group B-3 was given both MK and GA suspension gavage;Group B was given the same amount of saline gavage.The bronchoalveolar lavage fluid（BALF）of guinea pigs was taken within 24h after the end of the excitation phase,and the levels of TGF-β₁ and Smad₇ in BALF were determined by enzyme-linked immunosorbent assay（ELISA）Guinea pigs were sacrificed and airway remodeling was performed in lung tissue.Lung tissues were extracted and qRT-PCR was performed to detect the expression of TGF-β₁ and Smad₇ genes.The phim,total wall area（Wat）and smooth muscle area（Wam）of bronchial basement membrane in lung were measured by image analysis technique.Thymus was weighed and weighed.Results The pathological changes of bronchial smooth muscle and alveolar wall of group B,group B-1,group B-2 and group B-3 were significantly thicker than those of group A.Wat/phm,Wam/phm were higher than group A,and the levels of TGF-β₁ were higher than those of group A The levels of Smad₇ and Smad₇ in group B-1 were lower than that in group A（all P<0.05）.The pathological changes in group B-1,group B-2 and group B-3 were better than those in group B.Wat/phm and Wam/phm were lower than those in group B,TGF-β₁levels were lower than the B group,Smad₇ levels were higher than the B group,and B-3group compared with B-1 and B-2 group improved more（all P<0.05）;each group of thymus weight as a percentage of body weight was not significant Sex differences（P>0.05）.The expression of TGF-β₁ was negatively correlated with the expression of Smad₇.Negative correlation between TGF-β₁ mRNA and Smad₇ mRNA expression.The expression of TGF-β₁was positively correlated with normalized bronchial wall area（Wat/phm）and smooth muscle area（Wam/phm）The total wall area（Wat/phm）and smooth muscle area（Wam/phm）were negatively correlated（all P<0.001）.Conclusion The intervention of montelukast sodium and/or glycyrrhetinic acid can improve the imbalance of TGF-β₁ and Smad₇ expression levels,ultimately safely and effectively reduce airway remodeling in asthmatic guinea pigs;its mechanism may be through regulation of TGF-β₁/Smad₇ signal Transduction pathways;montelukast sodium and glycyrrhetinic acid are expected to play an important role in the prevention and treatment of airway remodeling in asthma.