A Study On The Mechanism Of The Effect Of Conditioned Immune Response On Mice With Bronchial Asthma

Objective(1)To observe the mechanism of the effect of conditioned immune response on mice with bronchial asthma;(2)To observe the therapeutic effect of conditioned immune response on mice with bronchial asthma;Methods An experimental asthma model was reproduced on healthy BALB/C mice(female,4-6 weeks old)sensitized and challenged with OVA.After that,all mice were divided into 7 groups randomly and treated as follows:Group A(CIR1 group)and group B(CIR2 group) established conditioned immune response by receiving the combination of conditioned stimulus(CS)and unconditioned stimulus(UCS)7times(7 days).The former used noise(85dB)as CS and the latter used SAC.Both groups nebulised budesonide plus salbutamol as UCS.Then,they received CS once a day and the combination of CS and UCS once a week for 20 weeks;Group C(conventional therapy group)nebulized budesonide and salbutamol once a day for 20 weeks;Group D(low-dose therapy group)nebulized budesonide and salbutamol once a day for the first 7 days,and then once a week for 20 weeks;Group E(noise group)suffered noise once a day for 20 weeks;group F(SAC group)received SAC once a day for 20 weeks; Group G(blank control group)nebulized PBS once a day for 20 weeks.All the groups above were challenged with OVA once a day.Group H(healthy control group) nebulized PBS once a day for 20 weeks.After the 20-week therapy,the bronchoalveolar lavage fluid(BALF)were collected to count EOS,the spleens were collected to pick up CD4⁺ T lymphocytes,detecte the expression of alpha 7 (nAChRα7),IL-4,IFN-γand IL-17,neuronal acetylcholine receptor,and analyze the relation among them,and the lungs were taken to observe the pathological changes by HE and MASSON staining.Results(1)After the 20-week therapy,the body weight of group D,E,F and G was much lower than that of group A,B,C and H.Meanwhile,the condition was much worse(P<0.01)(2)The percentage of EOS of group A,B and C was nuch lower than that of group G(8.67±1.23%vs 9.13±0.99%vs 8.40±1.12%vs 16.2±1.32%,t₁=16.13, t₂=16.58,t₃=17.44,P<0.01).(3)The expression ofnAChRα7 of group A,B and C were much lower than that of group G(12.30±0.96%vs 12.6±1.14%vs 14.72±0.94%vs 15.35±1.67%, t₁=7.81,t₂=6.51,t₃=7.62,P<0.01).(4)The expression of IL-4 of group A,B and C were much lower than that of group G(5.25±0.97%vs 4.73±0.80%vs 5.31±1.18%vs 12.26±1.31%,t₁ =16.68,t₂=19.03,t₃=15.30,P<0.01).(5)The expression of IL-17 of group A,B and C were much lower than that of group G(8.66±0.94%vs 8.49±0.69%vs 8.17±0.67%vs 18.61±1.18%,t₁=25.62, t₂=23.59,t₃=24.17,P<0.01).(6)The expression of IFN-γof group A,B and C were much higher than that of group G(18.04±1.05%vs 18.56±0.82%vs 18.13±0.96%vs 3.65±0.70%,t₁ =44.25,t₂=53.67,t₃=47.34,P<0.01).(7)There was no significanly difference in the expression of neuronal acetylcholine receptors between group A and B(nAChRα7:12.30±0.96%vs 12.6±1.14%,t=1.04, P>0.05;IL-4:5.25±0.97%vs 4.73±0.80%,t=1.09,P>0.05;IL-17:8.66±0.94%vs 8.49±0.69%,t=1.38;P>0.05;IFN-γ:18.04±1.05%vs 18.56±0.82%,t=0.11, P>0.05).(8)There was a positive correlation between nAChRα7 and IL-4(r=0.76,P< 0.01),a positive correlation between nAChRα7 and IL-17(r=0.46,P<0.01),and a negative correlation between nAChRα7 and IFN-γ,(r=0.69,P<0.01).(9)The airway epithelium tissue layer of group D,E,F and G was thicker than that of group H,while the lumen were narrower and inflammatory cells and collagen fibers were much more.In contrast,the airway epithelium tissue layer and infiltration of inflammatory cells were better in group A,B and C with therapy,ConclusionsConditioned immune response,which is estabolished by receiving the combination of either noise or SAC as CS and budesonide and salbutamol as UCS, can down-regulate the expression of nAChRα7 as well as regulate the immunological functions of CD4⁺ T lymphocytes to have the same therapeutic effect on the mice with brochial asthma.