引用本文:陈宇航1,2,张宁宁1,2,徐方蔚3,陈海鹏4,霍婧伟4,吴力群4.加味六安煎对咳嗽变异性哮喘豚鼠气道重塑关键通路及因子的影响[J].世界中医药,2023,(23):. |
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加味六安煎对咳嗽变异性哮喘豚鼠气道重塑关键通路及因子的影响 |
Effects of Modified Liu'an Decoction on Key Pathway and Factors Related to Airway Remodeling in Guinea Pigs with Cough Variant Asthma |
投稿时间:2023-01-09 |
DOI:10.3969/j.issn.1673-7202.2023.23.005 |
中文关键词: 加味六安煎 咳嗽变异性哮喘 转化生长因子-β 基质金属蛋白酶-9 Notch通路 关键基因 气道重塑 豚鼠 |
English Keywords:Modified Liu'an Decoction Cough variant asthma Transforming growth factor-β Matrix metalloproteinase-9 Notch signaling pathway Key genes Airway remodeling Guinea pigs |
基金项目:国家自然科学基金项目(81874487) |
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中文摘要: |
目的:研究加味六安煎对咳嗽变异性哮喘(CVA)豚鼠肺组织气道重塑关键因子转化生长因子-β(TGF-β)、基质金属蛋白酶-9(MMP-9)表达水平及Notch通路关键基因Notch受体1(Notch1)、δ样典型Notch配体1(Delta1)、锯齿状典型Notch配体1(Jagged1)、发状分裂相关增强子1(Hes1)表达的影响,探讨加味六安煎治疗CVA气道重塑的作用机制。方法:将30只雄性豚鼠随机分为正常对照组、CVA模型组、孟鲁司特钠组、加味六安煎低、中、高剂量组,每组5只。除正常对照组外,每组以卵蛋白(OVA)及氢氧化铝[Al(OH)3]腹腔注射致敏后以OVA雾化激发复制CVA模型,各组给予相应药物处理。观察肺组织病理形态,测定肺组织中TGF-β、MMP-9,检测肺组织中Notch1、Delta1、Jagged1及Hes1信使核糖核酸(mRNA)水平。结果:1)CVA模型组肺组织出现炎症细胞浸润,充血水肿,基底膜增厚,部分肺泡塌陷,各观察组中肺组织炎症细胞浸润、充血水肿等均不同程度减轻。2)CVA模型组中TGF-β、MMP-9表达水平较正常对照组升高;加味六安煎中、高剂量组TGF-β、MMP-9表达水平较CVA模型组均降低。3)CVA模型组与正常对照组比较,肺组织Notch1、Jagged1及Hes1 mRNA表达升高,Delta1 mRNA表达水平降低;与CVA模型组比较,加味六安煎高剂量组中Notch1、Jagged1、Hes1 mRNA降低,加味六安煎中、高剂量组中Delta1 mRNA表达升高。结论:加味六安煎可能通过调节Notch关键基因表达,改善T辅助细胞1/T辅助细胞2(Th1/Th2)失衡,减轻气道炎症,进而调节肺组织中TGF-β和MMP-9表达,改善气道重塑。 |
English Summary: |
This paper aims to observe the effect of modified Liu'an Decoction on the expression levels of key factors related to airway remodeling in lung tissue of guinea pigs with cough variant asthma (CVA),including transforming growth factor-β (TGF-β),matrix metalloproteinase-9 (MMP-9),notch receptor 1 (Notch1) of key genes in notch signaling pathway,δ-like typical notch ligand 1 (Delta1),zigzag typical notch ligand 1 (Jagged1),and hair division-associated enhancer 1 (Hes1),so as to investigate the mechanism of modified Liu'an Decoction in the treatment of CVA with airway remodeling.Methods:A total of 30 male guinea pigs were randomly divided into a normal group,a CVA model group,a montelukast sodium group,and low,medium,and high dose groups of modified Liu'an decoction,with five guinea pigs in each group.Except for the normal group,each group was sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminum hydroxide [Al(OH)3],and then the CVA model was reproduced by OVA atomization.Each group was given a corresponding drug treatment.The pathological morphology of lung tissue was observed,and TGF-β and MMP-9 in lung tissue were measured.The mRNA levels of Notch1,Delta1,Jagged1,and Hes1 in lung tissue were detected.Results:1) The CVA model group had inflammatory cell infiltration,hyperemia and edema,basement membrane thickening,and partial alveolar collapse in lung tissue,and the treatment group had different degrees of reduction in inflammatory cell infiltration and hyperemia and edema. 2) The expression levels of TGF-β and MMP-9 in the CVA model group were higher than those in the normal group,and the expression levels of TGF-β and MMP-9 in the middle and high dose groups of modified Liu'an Decoction were lower than those in the CVA model group.3) Compared with the normal group,the mRNA expression of Notch1,Jagged1,and Hes1 in lung tissue of the CVA model group was increased,and the mRNA expression level of Delta1 was reduced; compared with the CVA model group,the mRNA of Notch1,Jagged1,and Hes1 was lower in the high dose group of modified Liu'an Decoction,and the mRNA expression of Delta1 in the medium and high dose groups of modified Liu'an Decoction was increased.Conclusion:Modified Liu'an Decoction may improve Th1/Th2 cell imbalance and reduce airway inflammation by regulating the expression of key genes of Notch,thereby regulating TGF-β and MMP-9 expression in lung tissue and improving airway remodeling. |
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