Mechanisms Of Traditional Korean Medicine MaHuangDingChuan Decoction In Improving Airway Remodeling By Regulating NF-?B And MAPK Signaling Pathway In Asthmatic Mice

Objective:To explore the effect of Traditional Korean Medicine MaHuangDingChuan Decoction on ovalbumin-induced airway remodeling in asthmatic mice models,and provide experimental evidence for the clinical application of MaHuangDingChuan Decoction in the prevention and treatment of airway remodeling in asthma.Methods:Sixty seven-week-old clean grade BALB/c female mice were randomly divided into 5 groups,normal control group,asthma model group,MaHuangDingChuan Decoction low dose group,MaHuangDingChuan Decoction high dose group and dexamethasone positive control group.During the experiment,a mixture of 0.1 mg of ovalbumin and 4 mg of dry powder of aluminum hydroxide was used to sensitize the other 4 groups of mice except the normal control group on days 1,7,and 14,and the normal control group was intraperitoneally injected with 0.9%sodium chloride.Sodium is injected intraperitoneally.On the 21st day,the mice except the normal control group were inhaled with 3%OVA for 7 consecutive days to challenge the acute asthma,while the normal control group was inhaled with 0.9%sodium chloride.On the 32nd day,mice except the normal control group were given inhalation of 3%OVA three times a week for 4 weeks to stimulate the chronic phase of asthma,while the normal control group was inhaled with 0.9%sodium chloride.All treatment groups were given drugs by gavage before challenge from day 18.The normal control group and the asthma model group were replaced with 0.9%sodium chloride.Mice were sacrificed 24 hours after the last challenge.The lung tissue and bronchoalveolar lavage fluid(BALF)were collected.The pathological changes were observed by HE,PAS and MASSON staining.The contents of interleukin-4(IL-4),interleukin-5(IL-5),and interleukin-13(IL-13)were detected by enzyme-linked immunosorbent assay(ELISA).The effects of MaHuangDingChuan Decoction on the expression of NF-?B p65,p-ERK and p-p38MAPK protein in lung tissue of asthmatic mice were detected by immunohistochemical staining and Western blot.Results:1.The lung tissues of mice in each group were observed by HE and PAS staining,and it was found that in the model group,the structure of the connective tissue around the bronchi and blood vessels was disordered,there was a large number of lymphocytes and neutrophils in the tracheal lumen,the wall was thickened,the mucus was proliferated,and the airway mucosa was edematous;the above pathology was significantly improved in treatment groups compared with the model group.2.The results of ELISA showed that compared with the normal group,the contents of IL-4,IL-5,IL-13 in BALF of the model group were significantly higher and the IFN-y was significantly lower(P<0.05);the contents of IL-4,IL-5,IL-13 in BALF of each treatment group were lower than that of the model group,and the IFN-? content was increased,with significant differences(P<0.05).3.The expression level of NF-?Bp65 in the lung tissue was observed by immunohistochemistry.The results showed that in the model group,the nucleus was stained dark brown,and the expression of NF-?Bp65 protein was significantly increased compared with the normal group;compared with the model group,there was a small amount of nuclei stained dark in treatment groups,and the expression level of NF-?Bp65 protein was greatly reduced.4.The protein contents of p-ERK,p-p38MAPK and NF-?Bp65 were detected by Western blot.The results showed that the expression of p-ERK,p-p38MAPK and NF-?Bp65 in the model group was significantly higher than that in the normal group,and the difference was significant.The expression of p-ERK,p-p38MAPK and NF-?Bp65 in treatment groups were lower than that in the model group,and the decrease was greater in the high dose group.Conclusions:1.MaHuangDingChuan Decoction can alleviate airway remodeling in bronchial asthmatic mice,and the effect is more obvious in the high dose group.2.MaHuangDingChuan Decoction can down-regulate the contents of infla mmatory cytokines IL-4,IL-5,IL-13,up-regulate the content of IFN-?,thus re gulate the balance of Th1/Th2,inhibit airway remodeling in asthmatic mice,an d the mechanism may be related to down-regulation of the expression of NF-?Bp65,p-ERK,p-p38 MAPK.