二陈汤加味调控Hedgehog(HH)信号通路作用于慢性阻塞性肺疾病炎症的机制OA
Modified Erchentang Inhibits Inflammation in Chronic Obstructive Pulmonary Disease via Hedgehog(HH)Signaling Pathway
目的:基于刺猬(HH)信号通路,探讨二陈汤加味对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)炎症的作用机制.方法:香烟烟熏联合气管滴注脂多糖(LPS)法制备 COPD 大鼠模型.测定大鼠肺功能;采用酶联免疫吸附测定法(ELISA)测定血清中白介素-4(IL-4)和 IL-13 的含量;实时荧光定量聚合酶链式反应(Real-time PCR)法测定音猬因子(Shh)、跨膜蛋白受体 1(Ptch1)、神经胶质瘤相关癌基因同源物 1(Gli1)mRNA 表达;免疫组织化学(IHC)法检测细胞 HH 信号通路相关因子 GLI1、SHH、PTCH1 蛋白阳性表达;HE 染色观察大鼠肺组织形态学变化.结果:与正常对照组比较,模型对照组大鼠第一秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC 显著降低(P<0.01),血清 IL-4 和 IL-13 含量显著升高(P<0.01),肺组织 Shh、Ptch1 和 Gli1 mRNA 和蛋白阳性表达显著上调(P<0.01);与模型对照组相比,环巴胺组、二陈汤加味 10、20 g/kg 组 FEV1/FVC、FEV1、FVC 明显增高(P<0.05 或 P<0.01),二陈汤加味5、10、20 g/kg 组及环巴胺组血清 IL-4 和 IL-13 的含量显著降低(P<0.01),肺组织 Shh、Ptch1 和 Gli1 mRNA 及蛋白表达下调(P<0.05 或 P<0.01).结论:香烟烟熏联合气管滴注 LPS 法所致的 COPD 模型大鼠 HH 信号通路被显著激活,HH 信号通路相关因子表达上调;二陈汤加味可能通过抑制 Shh、Ptch1 和 Gli1 mRNA 表达,从而抑制 HH 信号通路下游调节因子 GLI1 活化,减少 IL-4 和IL-13 的释放,从而抑制 COPD 炎症反应.
Objective:To explore the therapeutic mechanism of modified Erchentang(二陈汤)on inflammation in chronic obstructive pulmonary disease(COPD)via the Hedgehog(HH)signaling pathway.Methods:The rat model of COPD was established by cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide(LPS).The serum levels of interleukin-4(IL-4)and interleukin-13(IL-13)were measured by enzyme-linked immunosorbent assay.The mRNA levels of sonic hedgehog(Shh),patched 1(Ptch1),and glioma-associated oncogene homolog 1(Gli1)were determined by real-time PCR.The protein levels of HH signaling pathway-related factors GLI1,SHH,and PTCH1 in cells were detected by immunohistochemistry.Hematoxylin-eosin staining was conducted to reveal the morpho-logical changes of the rat lung tissue.Results:Compared with the normal control group,the model control group showed reduced forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),and FEV1/FVC ratio(P<0.01),elevated serum levels of IL-4 and IL-13(P<0.01),and up-regulated mRNA and protein levels of Shh,Ptch1,and Gli1 in the lung tissue(P<0.01).Compared with the model control group,the cyclopamine group and the modified Erchentang(20,10 g/kg)groups showed increases in FEV1/FVC ratio,FEV1,and FVC(P<0.05 or P<0.01).The modified Erchentang(5,10,and 20 g/kg)groups and the cyclopamine group showed declined serum levels of IL-4 and IL-13(P<0.01)and down-regulated mRNA and protein levels of Shh,Ptch1,and Gli1 in the lung tissue(P<0.05 or P<0.01).Conclusion:The HH signaling pathway was significantly activated in the rat model of COPD induced by ciga-rette smoke exposure combined with intratracheal instillation of LPS,with up-regulated expression of HH signaling path-way-related factors.Modified Erchentang may inhibit the activation of the downstream regulatory factor GLI1 of the HH signaling pathway by down-regulating the mRNA levels of Shh,Ptch1,and Gli1,thereby reducing the release of IL-4 and IL-13 and inhibiting the inflammation in COPD.
任鹏飞;季书;刘欢欢;尚立芝;赵晗方;王栋梁;尚皓梵;王琦
郑州西亚斯学院医学院,郑州 451100河南科技职业大学,周口 466000河南医学高等专科学校,郑州 451191河南中医药大学,郑州 450046郑州西亚斯学院医学院,郑州 451100郑州西亚斯学院医学院,郑州 451100河南中医药大学,郑州 450046河南中医药大学,郑州 450046
二陈汤慢性阻塞性肺疾病刺猬信号通路炎症跨膜蛋白受体1神经胶质瘤相关癌基因同源物1(GLI1)
ErchentangChronic obstructive pulmonary diseaseHedgehog signaling pathwayInflammationPatched 1(PTCH1)Glioma-associated oncogene homolog 1(GLI1)
《中药药理与临床》 2026 (4)
29-34,50,7
国家自然科学基金面上项目(编号:81573881)河南省科技攻关项目(编号:182102311163)河南省高等学校重点科研项目(编号:25B360003)郑州西亚斯学院2024年度科研资助项(编号:2024XKD081,2024XKD094)
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