甘草次酸对咳嗽变异性哮喘小鼠Th1/Th2平衡影响的研究

Effect of glycyrrhetinic acid on Th1/Th2 balance in cough variant asthma mice

目的:观察甘草次酸对咳嗽变异性哮喘小鼠Th1/Th2平衡的影响,并初步探讨其减轻肺部炎症的作用机制。方法:将48只雌性幼龄BALB/c小鼠,分为空白对照组、模型对照组、醋酸泼尼松组(5 mg/kg)、甘草次酸高剂量组(20 mg/kg)、甘草次酸中剂量组(10 mg/kg)及甘草次酸低剂量组(5 mg/kg),每组8只。采用卵蛋白(OVA)诱导的方法建立咳嗽变异性哮喘模型,给予药物治疗后观察动物哮喘行为学;计算肺脏指数;采用ELISA法测定肺泡灌洗液中OVA-sIgE水平;采用HE染色观察肺组织病理变化;Western blot法检测肺组织中T-bet、IFN-γ、Gata3、IL-4、IL-13的蛋白表达。结果:与模型对照组相比,醋酸泼尼松和甘草次酸组小鼠肺脏指数、肺泡灌洗液中OVA-sIgE水平及肺组织中的Th2相关因子表达情况均明显降低(P<0.05或P<0.01),肺组织中的Th1相关因子表达情况明显升高(P<0.05),肺组织的病理情况有所改善。结论:甘草次酸对咳嗽变异性哮喘小鼠有治疗作用,其机制可能与调节肺组织中Th1/Th2有关。

Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female BALB/c mice were divided into Control,CVA,Prednisone Acetate,Glycyrrhetinic Acid high-dose,Glycyrrhetinic Acid middle-dose and Glycyrrhetinic Acid low-dose groups randomly,with 8 mice in each group.The CVA mice model was established by ovalbumin(OVA)sensitization and OVA challenge,the animal asthma behavior was observed after drug administration,and the index of lung of mice were recorded.The level of OVA-sIgE in the bronchoalveolar lavage fluid(BALF)was tested by ELISA.The pathological changes of the lung tissue were observed by Hematoxylin and Eosin(HE)staining.The protein expressions of T-bet,IFN-γ,Gata3,IL-4 and IL-13 in the lung tissue were determined by Western blot.Results:Compared with the CVA group,the index of lung of mice,the OVA-sIgE level in BALF and expression levels of Th2-related factor in the lung tissue of mice in Prednisone Acetate and Glyc-yrrhetinic Acid groups were significantly decreased(P<0.05 or P<0.01),the infiltration of inflammatory cells in the lung tissue was reduced,while expressions of Th1-related factor in the lung tissue was significantly increased(P<0.05).Conclusion:Glycyrrhetinic acid has therapeutic effect on CVA mice,the underlying mechanism of Glycyrrhetinic acid alleviating lung impairment and airway inflammation may be associated with mediating the Th1/Th2 imbalance in the lung tissue.