The Influences of Airway Tissue Injury,Serum Th1/Th2 Cytokines and TLR4/NF-κB Signal Pathway by Ghrelin in Asthma Rats
Objective:To explore the mechanism of Ghrelin on airway tissue injury and serum Th1/Th2 cytokines in asthma model rats via Toll like receptor 4(TLR4)/nuclear transcription factors-κB(NF-κB)signal pathway.Methods:A total of 40 healthy Wistar male rats with average age of 7 weeks(average weight of 220 g)were randomly divided into 4 groups,with 10 rats in each group,they were control group,model group,low concentration group of Ghrelin(1 μmol/L)and high concentration group(5 μmol/L).In addition to the control group,the other three groups replicated acute asthma models.The low concentration and high concentration groups of Ghrelin were intraperitoneally injected with 10 mL/kg,while the control group and model group were injected with equal amount of physiological saline.After 24 hours of modeling,asthma symptom score of each group rats were evaluated,the percentages serum neutrophils and lym-phocytes were measured,then neutrophils to lymphocytes ratio(NLR)was calculated,serum IgE,Th1 cytokine IFN and Th2 cytokine IL-4 were detected by ELISA method,then IFN-γ/IL-4 was calculated,lung tissue was stained with HE to calculate airway wall thick-ness and tracheal smooth muscle thickness,for airway injury degree was evaluated,Western blot method was to detect TLR4 and NF-κB p65 proteins relative expression in lung tissue.Results:Compared with the control group,the asthma symptom score,lymphocyte per-centage,IgE,IL-4,airway wall thickness and tracheal smooth muscle thickness,TLR4 and NF-κB p65 protein relative expression levels in the model group rats were significantly higher,while NLR,IFN-γ and IFN-γ/IL-4 were significantly lower(P＜0.05).Compared with the model group,the asthma symptom score,lymphocyte percentage,IgE,IL-4,airway wall thickness,tracheal smooth muscle thickness,TLR4,and NF-κB p65 protein relative expression levels in the low and high concentration groups of Ghrelin were significantly less,while NLR,IFN-γ and IFN-γ/IL-4 were significantly more(P＜0.05).Compared with the low concentration group,above indicators in the high concentration group were also significantly differen(P＜0.05).Conclusion:Ghrelin may inhibit TLR4/NF-κB signal pathway activity to improve asthma symptom,reduce inflammatory,regulate Th1/Th2 balance,alleviate airway tissue injury,and exhibit a certain concentra-tion dependence.Ghrelin is expected to become a new pathway for clinical intervention in asthma.
GhrelinAsthmaToll like receptor 4Nuclear transcription factor-κBAirway injuryTh1/Th2 cytokines
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