Improvement effects of vitexin on asthmatic model mice based on Notch signaling pathway

FEI Yuanyuan; GE Mingkun; BIAN Qingping

doi:10.6039/j.issn.1001-0408.2024.15.09

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Improvement effects of vitexin on asthmatic model mice based on Notch signaling pathway

更新时间：2025-09-23

- Improvement effects of vitexin on asthmatic model mice based on Notch signaling pathway
- ZHONGGUO YAOFANG Vol. 35, Issue 15, Pages: 1849-1854(2024)
- 作者机构：
  
  1.东南大学附属中大医院江北院区感染科，南京　210044
  2.东南大学附属中大医院江北院区呼吸科，南京　210044
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.15.09
  CLC： R965
- Received：08 April 2024，
  
  Revised：2024-06-24，
  
  Accepted：26 June 2024，
  
  Published：15 August 2024
- 稿件说明：
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费园园,葛明坤,卞庆平.基于Notch信号通路探讨牡荆素对哮喘模型小鼠的改善作用 [J].中国药房,2024,35(15):1849-1854.

FEI Yuanyuan,GE Mingkun,BIAN Qingping.Improvement effects of vitexin on asthmatic model mice based on Notch signaling pathway[J].ZHONGGUO YAOFANG,2024,35(15):1849-1854.
费园园,葛明坤,卞庆平.基于Notch信号通路探讨牡荆素对哮喘模型小鼠的改善作用 [J].中国药房,2024,35(15):1849-1854. DOI： 10.6039/j.issn.1001-0408.2024.15.09.

FEI Yuanyuan,GE Mingkun,BIAN Qingping.Improvement effects of vitexin on asthmatic model mice based on Notch signaling pathway[J].ZHONGGUO YAOFANG,2024,35(15):1849-1854. DOI： 10.6039/j.issn.1001-0408.2024.15.09.

摘要

目的

基于Notch信号通路探究牡荆素对哮喘模型小鼠的改善作用及机制。

方法

采用卵清蛋白与氢氧化铝混悬液腹腔注射和卵清蛋白雾化激发的方法构建哮喘小鼠模型。将哮喘小鼠随机分为模型组、牡荆素组（40 mg/kg）、Notch激活剂组（1 mg/kg Jagged1）、牡荆素+Notch激活剂组（40 mg/kg牡荆素+1 mg/kg Jagged1），每组12只；另取12只小鼠设为对照组。各组小鼠灌胃/腹腔注射相应药物或生理盐水，每天1次，连续14 d。末次给药后，检测小鼠静息每分钟通气量（VE）、呼气峰流速（PEF），观察肺组织病理形态并检测纤维化变性情况，测定外周血中辅助性T细胞17（Th17）、调节性T细胞（Treg）比例并计算Th17/Treg值，测定血清中白细胞介素18（IL-18）、IL-6、IL-17、IL-10水平，检测肺组织中Notch1、Delta样配体4（DLL4）、发状分裂相关增强子1（Hes1）蛋白表达。

结果

与对照组比较，模型组小鼠肺组织发生严重病理损伤及炎症细胞浸润；VE、PEF、外周血中Treg细胞比例、血清中IL-10水平均显著降低（

＜0.05）；肺组织中胶原容积分数（CVF），外周血中Th17细胞比例、Th17/Treg值，血清中IL-18、IL-6、IL-17水平，肺组织中Notch1、DLL4、Hes1蛋白表达水平均显著升高（

＜0.05）。与模型组比较，牡荆素组小鼠肺组织病理损伤明显改善，上述指标变化趋势被显著逆转（

＜0.05），且Notch激活剂Jagged1可显著逆转牡荆素对哮喘小鼠的上述药理功效（

＜0.05）。

结论

牡荆素可通过抑制Notch信号通路，改善哮喘小鼠肺功能、Th17/Treg免疫失衡及炎症反应，减轻肺组织病理损伤及纤维化。

Abstract

OBJECTIVE

To explore the improvement effect and mechanism of vitexin on asthmatic model mice based on Notch signaling pathway.

METHODS

Asthma model of mice was established by intraperitoneal injection of ovalbumin and aluminum hydroxide suspension and nebulization stimulation of ovalbumin， and randomly divided into model group， vitexin group （40 mg/kg）， Notch activator group （1 mg/kg Jagged1）， vitexin+Notch activator group （40 mg/kg vitexin+1 mg/kg Jagged1）， with 12 mice in each group. Another 12 mice were selected as the control group. Each group received intragastric/intraperitoneal injection of relevant medicine or normal saline， once a day， for consecutive 14 days. After the last medication， minute ventilation at rest （VE） and peak expiratory flow （PEF） were detected in mice； the pathological morphology of lung tissue and fibrosis degeneration were observed and determined. The proportion of T helper cell 17 （Th17） and T regulatory cell （Treg） in peripheral blood were detected， and the Th17/Treg ratio was calculated. The levels of serum inflammatory factors interleukin （IL）-18， IL-6， IL-17 and IL-10 were determined， and the expressions of Notch1， Delta-like ligand 4 （DLL4）， hairy and enhancer of split 1 （Hes1） in lung tissue were detected.

RESULTS

Compared with the control group， serious pathological injury and inflammatory cell infiltration occurred in the lung tissue of mice in the model group， while VE， PEF， the proportion of Treg cells in peripheral blood and serum level of IL-10 were significantly reduced （

＜0.05）； collagen volume fraction （CVF） in lung tissue， Th17 cells proportion and Th17/Treg ratio in peripheral blood， serum levels of IL-18， IL-6 and IL-17， and the protein expressions of Notch1， DLL4 and Hes1 in lung tissue were significantly increased （

＜0.05）. Compared with the model group， the pathological injury of lung tissue in vitexin group was significantly improved compared with model group， and the changing trend of the above indexes was reversed （

＜0.05）； Notch activator Jagged1 could significantly reverse the pharmacological effects of vitexin on asthmatic mice （

＜0.05）.

CONCLUSIONS

Vitexin can improve lung function， Th17/Treg immune imbalance and inflammatory response， and alleviate pathological injury and fibrosis of lung tissue in asthmatic mice by inhibiting the Notch signaling pathway.

关键词

Keywords

references

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