目的 基于分子对接技术探讨甘草次酸对咳嗽变异性哮喘小鼠Th2偏移的纠正作用，探讨其治疗咳嗽变异性哮喘的可能性。 方法 利用Autodock Vina软件进行分子对接。将小鼠按随机数字表法分为空白对照组、模型组、醋酸泼尼松组及甘草次酸高、中、低剂量组，每组8只。除空白对照组外，其余各组采用卵蛋白诱导的方法建立咳嗽变异性哮喘模型。甘草次酸高、中、低剂量组灌胃甘草次酸混悬液20、10、5 mg/kg，醋酸泼尼松组灌胃醋酸泼尼松5 mg/kg，空白对照组和模型组灌胃等体积的生理盐水。1次/d，连续14 d。观察各组小鼠行为；采用阿利新蓝-过碘酸希夫染色观察肺组织支气管黏液分泌情况；计算小鼠脾脏指数；采用Western blot法检测脾组织中Gata结合蛋白3（Gata3）、IL-4、IL-13蛋白表达。 结果 分子对接结果表明，甘草次酸与Th2相关因子Gata3、IL-4和IL-13有较好的结合活性。动物实验结果表明，与模型组比较，甘草次酸各剂量组小鼠肺组织黏液分泌减少，甘草次酸低剂量组脾脏指数降低，甘草次酸高、中、低剂量组IL-4、IL-13表达降低（P<0.05），甘草次酸中、低剂量组Gata3表达降低（P<0.05）。 结论 甘草次酸可纠正咳嗽变异性哮喘小鼠免疫系统Th2的偏移，具有一定的治疗作用。 Objective To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique To explore the possibility of its treatment for cough variant asthma. Methods The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot. Results Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased (P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased (P<0.05). Conclusion Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.
Discussion on the effects of glycyrrhetinic acid on cough variant asthma mice by adjusting Th2 deviation based on molecular docking technique
Objective To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique To explore the possibility of its treatment for cough variant asthma. Methods The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot. Results Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased (P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased (P<0.05). Conclusion Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.
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