| BackgroundAsthma is characterized by airway hyperresponsiveness associated with bronchial inflammation. Recently, a lot of evidences show that endogenous glucocorticoids play an important role in modulation of airway responses to antigen challenge, our previous studies have shown hyporesponsiveness of Hypothalamic-Pituitary-Adrenal Axis (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.In many clinical researches, COPD with AHR patients using glucocorticoids can get some effects, we think COPD with AHR models exist the dysfunction of HPAA.Objective: To study the relationship between COPD with AHR and NEI, to study the changes of HPAA and several related cytokines in COPD and COPD with AHR models, to observe the effects of Chinese herbs on them.Methods: All experiments were divided into 2 parts.Part one: 48 Brown Norway(BN) mice were divided into 4 groups:Group A were COPD with AHR models which were stimulated by ovalbumin(OVA), cigarettes and lipopolysaccharide(LPS);Group B were allergic asthma models which were challenged by ovalbumin(OVA);Group C is control group(nothing on it);Group D were COPD models which were challenged by cigarettes and LPS.Blood samples, lung function, airway hyperreponsiveness, BALF and hypothalam tissue were taken at the last day. IL-6, IL-8, IL-4, IL-5, IFN-γ, TNF-α, ACTH, CRHmRNA, CORT were measured in all groups.Part two:72 BN mice were randomly divided into 6 groups(E, F, G, H, L, M group) E, F, G groups(COPD models) were challenged by cigarettes and LPS; H,L, M groups(COPD with AHR models) were sensitized with OVA, smoking and LPS.E,F,G were administered by low, moderate and high dose Chinese herbal respectively to regulate the HPAA of COPD models. H,L,M were administered by low, moderate and high dose Chinese herbal respectively to regulate the HPAA of COPD with AHR models.Results:Part one : At first, according to the results of measuring lung function and airway hyperresponsiveness, COPD with AHR models were success.1. Changes of HPAA:1.1 There is no significance of CRHmRNA among 4 groups(P＞0.05); The significant difference is between asthma groups and COPD groups(P＜0.05);When normal groups compare COPD groups, there is the significance between them. (P＜0.01).CRHmRNA of COPD with AHR is lowest among them.1.2 There is no change of ACTH among 4 groups(P＞0.05);1.3 The difference of serum CORT was seen among 4 groups(P＜0.05); Serum CORT of COPD and COPD with AHR were both low.2. Changes of Cytokines:2.1 In serum, there is no difference of IL-4among 4 groups(P＞0.05);Abig change can be seen between COPD with AHR groups and COPD groups(P＜0.05).2.2 As to serum IL-5, it is significant that be seen among 4 groups (P＜0.01),that is to say, it has an increase trend among 4 groups. The difference exits between asthma group and COPD group(P＜0.01); The same condition exits between COPD group and control group(P＜0.05). In bronchoalveolar lavage fluid, there was a significant increase in COPD with AHR group compared with asthma group. (P＜0.01)2.3 There is no changes of serum IL-6 among 4 groups(P＞0.05);In bronchoalveolar lavage fluid, The significance can be seen between asthma group and COPD group(P＜0.05);At the same time, there is a big change between COPD with AHR group and COPD group(P＜0.01).The significance exits 4 groups(P＜0.01), and we can see an increase trend among them.2.4 There is no difference of serum IL-8 among 4 groups(P＞0.05);However, when asthma groups compared with COPD groups and normal groups respectively, the difference was found between them. (P＜0.01) serum IL-8 of asthma groups was the highest in these three groups. In bronchoalveolar lavage fluid, a big change was seen between COPD with AHR groups and asthma groups (P＜0.01), meanwhile, there is significance between asthma groups and COPD groups. (P＜0.01)2.5 There is no changes of serum TNF-αamong 4 groups(P＞0.05); The significance was found between COPD with AHR group and asthma group(P＜0.01), In bronchoalveolar lavage fluid, the change can be seen COPD group in compared with control group. (P＜0.01)2.6 There is no changes of serum IFN- y among 4 groups(P＞0.05); In bronchoalveolar lavage fluid, The difference was seen between asthma group and control group(P＜0.01). Meanwhile, the same situation exits between COPD group and control group(P＜0.05)3. Changes of Lung FunctionLung function of control group is the best. Asthma group compared with control group, there is a big change between them, P＜0.05, Iung function of A, B, D group were worser than control group.Part Two1. Changes of HPAA1.1 According to COPD, there is significance of CRHmRNA among 3 different Chinese herbal formular groups(P＜0.01), it showed a decline with the increase of dose among group E, F, G .However, according to COPD with AHR, firstly, there is a decrease at moderate dose, then an increase trend appeared following increasing dose.1.2 There is no changes of ACTH among E, F, G groups. (P＞0.05) However, there is changes of ACTH among H, L, M groups. (P＜0.05) Following the dose increasing, ACTH showed a declined trend.1.3 There are effects of 3 different Chinese herb on COPD modelgroup(P＜0.05), The serum CORT of group F is the top in these three groups. According to COPD with AHR, serum CORT showed an increase trend with the increase of dose among group H, L, M. (P＜0.01)2. Changes of Cytokines2.1 In serum IL-4, there is a big change among group E,F,G,C,D(P＜0.05), as the dose increasing, serum IL-4 has a declined trend. According to COPD with AHR, we can see the same situation among group H,L,M,A,C(P＜0.01). Serum IL-4 showed a decrease when the dose is increased.2.2 To serum IL-5, we can see the difference between group M and normal group. (P＜0.01); In bronchoalveolar lavage fluid, group E compared with group F, the significance we can see exits between them. (P＜0.05)2.3 There is a big change of serum IL-6 among E,F,G(P＜0.01), as the dose increasing, serum IL-6 were decreased. There is a significant change of lavage fluid IL-6 among H,L,M(P＜0.05), when using moderate dose, IL-6 became the lowest.2.4 According to lavage fluid IL-8, there is the difference of IL-8 among E,F,G,D(P＜0.05), when using the high dose, IL-8 were declined to the bottom. When group H,L,M compared respectively, the significance was found(P＜0.05).2.5 When group E,F,G,C,D compared, the decrease trend of serum TNF-αwas found when the dose were increased(P＜0.05).In lavage fluid, when E,F,G compared, the difference was found(P＜0.05), among them, the moderate dose can let TNF-αreach the lowest. There is the significance among H,L,M(P＜0.05), as the dose increased, TNF-αwere found showing a decreasing trend.2.6 There is a big change of serum IFN-γamong group E,F,G,C(P＜0.01), serum IFN-γwere lowered by the dose increased. At the same time, the difference was found among group H,L,M(P＜0.05).In lavage fluid, among group E,F,G, we can find the difference(P＜0.05), then we can find the significance of IFN-γamong group H,L,M(P＜0.05), and two groups compared respectively, the changes were found(P＜0.01)3. Changes of Lung FunctionThere is no change among group E,F,G, There is significance among group H,L,M, Busbenyiqi Chinese herb can regulate lung function of COPD with AHR.Conclusion:COPD with AHR models had the dysfunction of HPAA; it is importance of Th2 in the progress of airway inflammation coming into being. IL-8,1L-6, TNF-αoppcupied important situation at the COPD's progress of airway inflammation; Chinese herb of Bushenyiqi can regulate the dysfunction of HPAA. At the same time, Chinese herb can regulate lung function of COPD with AHR.
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