摘要
目的考察桔梗汤总黄酮(FPG)对慢性阻塞性肺病(COPD)大鼠的治疗作用,研究其对TLR4/TRIF/IRF3和TLR4/MyD88通路的影响,探讨其治疗COPD可能的分子机制。方法建立COPD大鼠模型,将60只SD大鼠分为空白组、模型组、阳性对照组及不同剂量的桔梗汤总黄酮治疗组,经过3周治疗后,通过分析大鼠肺功能指标、肺灌洗液中IL-6、IL-12、TNF-α的含量、血清中IFN-α、IFN-β的含量、肺组织病理切片及MyD88、TLR4、TRAM、TRIF、TRAF6、IRF3、P-IRF3蛋白表达量变化,探讨桔梗汤总黄酮防治COPD的分子机制。结果各个剂量组的桔梗汤总黄酮均可明显缓解COPD模型大鼠的肺部通气功能,可显著抑制COPD大鼠肺灌洗液中IL-6、IL-12、TNF-α的含量,抑制其血清中IFN-α、IFN-β的含量,以上结果均呈现明显的剂量依赖性;Western blot实验结果表明,桔梗汤总黄酮对COPD大鼠肺组织中的MyD88无显著影响,但可显著降低其中TLR4、TRAM、TRIF、TRAF6、IRF3、P-IRF3蛋白表达,差异具有统计学意义。结论桔梗汤总黄酮治疗COPD可能是通过抑制TLR4/TRIF/IRF3通路发挥作用,不是通过TLR4/MyD88经典通路实现的。
Objective To investigate the effect of FPG on the TLR4/TRIF/IRF3 pathway and TLR4/MyD88 pathway of COPD rats, to explore the molecular mechanism of its prevention and treatment of COPD.Methods We established a COPD rat model, divided 60 SD rats into a blank group, a model group, a positive control group and different doses of the total flavonoids treatment group of Jiegeng decoction. After 3 weeks of treatment, through the analysis of rat lung function indicators, the content of IL-6, IL-12, and TNF-α in the lung lavage fluid, the content of IFN-α and IFN-β in the serum, pathological sections of lung tissue and changes in protein expression of MyD88, TLR4, TRAM, TRIF, TRAF6,IRF3, and P-IRF3, we explored the molecular mechanism of total flavonoids in Jiegeng decoction to prevent and treat COPD.Results FPG in each dose group could obviously alleviate the lung ventilation function of COPD model rats,could significantly inhibit the content of IL-6, IL-12 and TNF-α in the lung lavage fluid of COPD rats, could inhibit the content of IFN-α and IFN-β in its serum, and the above results showed a significant dose-dependent. The results of Western blot showed that FPG had no significant effect on MyD88 in the lung tissue of COPD rats, but it could significantly reduce the protein expression of TLR4, TRAM, TRIF, TRAF6, IRF3, and P-IRF3, and the difference was statistically significant.Conclusion FPG may prevent COPD not through the classic TLR4/MyD88 pathway, but through the inhibition of the TLR4/TRIF/IRF3 pathway.
作者
张超云
郝鹏飞
丁生晨
张仲鸣
Zhang Chaoyun;Hao Pengfei;Ding Shengchen;Zhang Zhongming(Nanyang Institute of Technology,Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Nanyang 473000,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2022年第4期1495-1502,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
河南省科学技术厅科技攻关项目(172102310218):基于 MUC5AC、EGFR、TNF-α 表达的桔梗汤有效部位群对干预慢性阻塞性肺疾病模型大鼠的实验研究,负责人:张超云。
