Dysfunction Of NEI In Asthma Models And The Effects Of Bushenyiqi Tang On It

Background: asthma is characterized by airway hyperresponsiveness associated with bronchial inflammation, it is well accepted that the Th2 cytokines play an important role in the pathogenesis of allergic asthma,but it only emphasized the mechanism of inflammation and ignored the body protective mechanism. Recently, growing evidences show that endogenous glucocorticoids play an important role in modulation of airway responses to antigen challenge,but the changes of hypothalamo-pituitary-adrenal axis (HPAA) in different course of asthma is unknown.According to our past experiments, some Chinese herbal formula Busheyiqi tang can improve the responsiveness of HPAA in the state of stress.whether it can treat asthma by this way is unknown.Objective: to understand the changes of HPAA and some cytokines in different course of asthma model ,to determine the effect of bushenyiqi tang on HPA in asthma model. Methods: all experiments were divided into 2 part.Part one :40 BN mice were randomly divided into 5 groups. Group A is control group which were sensitised and challenged with saline. Group B, C, D and E were allergic asthma models which were challenged by ovalbumin (OVA) respectively for lday,7days ,7days following 7days without challenge , 7days following 7days without challenge then challenged 7 days again(20 minutes a day). Blood samples and hypothalam tissue were taken at the last day of challenging by OVA. IL-6, ACTH, CRHmRNA, CORT, IL-4, IFN—γ were mersured in all groups.Part two : 32 BN mouses were randomly divided into 4 groups.All animals were sensitised and challenged with OVA for 7days following 7days without challenge then challenged 7 days again(20 minutes a day). Group G, H and I were administered by low,moderate and high dose Chinese herbal formula bushenyiqi tang respectivelyfrom day 21 to day 35.Group F were treated with saline instead of Chinese herbal formula. How the samples were taken and measured is as above. Results: Part one1. Changes of HPAA:The difference of CRHmRNA was significant among 5 groups (P<0. 01). The higher level of CRHmRNA was seen in group B than group A significantly (P<0. 01) the lower level of CRHmRNA was seen in group C, D, E respectively than group B significantly (P<0.01) .The difference of ACTH is significant among 5 groups (P<0. 05). The increase trend but no significant difference was shown in group B comparison with group A.There was a significant decrease in group E in comparison with group B and D (P<0.05).2. Changes of cytokinesThere was a significant difference in IL-4, IFN— γ , IL-6 among 5 groups (P<0. 01).The higher concentration of IL-4 was seen in group C, D, E respectively than group B significantly (P<0.05 ) . The concentration of IL-4 in group D, E was significantly increased in comparison with that of group A. (P<0.05) .The lower concentration of IFN— γ was seen in group C, D respectively than that of group B significantly (P<0. 01). The concentration of IFN—γ in group D was significantly decreased in comparison with that of group A. (P<0.05)the higher concentration of IL-6 was significantly seen in group E than group A, B, C,D respectively (P<0.05) .there was a significant increase of IL-6 in group C(P<0.05) and D(P<0.01) respectively than that of group B. 3.The correlation of IL-6 and HPAAThere was a significant inverse correlation between serum IL-6 and plasma ACTH (r=-0.325).4.The correlation of IL-4 and IFN— γ :There was a significant inverse correlation between serum IL-4 and IFN— γ (r= -0.339).Part two1.The effect of bushenyiqi tang on HPAACRHmRNA, ACTH, CORT showed an increase trend with the increase of dose among these 3 groups.There was a significant difference of CRHmRNA between group I and group F.the higher expression of CRHmRNA was showed in group I and group H than that of group G (P <0.05 ). Plasma ACTH was significantly increased in group H and I respectively than that of group F and G (P <0.05 ). There was a significantly increase in CORT of group I than that of group F( P<0.05). 2.The effect of bushenyiqitang on cytokinesThere was no significant difference among these 4 groups.But comparison betweenevery 2 groups showed that IFN— γ was significantly decreased in group H thangroup F.Conclusion: the function of HPAA is upregulated in inaugural attack of asthma. But it shows hyporesponsiveness of HPAA in chronic asthma models after repeated attacks, accompany with the increase of the production of IL-4 , IL-6 and decrease of the production of IFN—γ .IL-6 probably plays an important role in modulation of HPAA.Traditional Chinese medicine bushenyiqi formula can improve the hyporesponsiveness of HPAA in a dose dependent matter, .it suggest that the target of bushenyiqi formula locate in hypothalamus or above.We conclude that bushenyiqi formula can be used to treat asthma. It can reduce the dose and side effects of glucocorticoids when both this formula and glucocosteroids are administered to asthma patients, the results show a bright future in the treatment of asthma.