Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD

WANG Yaru; XU Peipei; LI Shirong

doi:10.6039/j.issn.1001-0408.2025.18.06

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Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD

更新时间：2025-09-25

- Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD
- ZHONGGUO YAOFANG Vol. 36, Issue 18, Pages: 2250-2255(2025)
- 作者机构：
  
  1.东南大学附属中大医院江北院区呼吸与危重症医学科，南京　210044
  2.南京鼓楼医院血液科，南京　210008
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.18.06
  CLC： R965;R285.5
- Received：12 March 2025，
  
  Revised：2025-07-14，
  
  Accepted：06 August 2025，
  
  Published：30 September 2025
- 稿件说明：
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王亚茹,许佩佩,李士荣.白花丹素对AECOPD大鼠炎症反应及氧化应激的影响及机制[J].中国药房,2025,36(18):2250-2255.

WANG Yaru,XU Peipei,LI Shirong.Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD[J].ZHONGGUO YAOFANG,2025,36(18):2250-2255.
王亚茹,许佩佩,李士荣.白花丹素对AECOPD大鼠炎症反应及氧化应激的影响及机制[J].中国药房,2025,36(18):2250-2255. DOI： 10.6039/j.issn.1001-0408.2025.18.06.

WANG Yaru,XU Peipei,LI Shirong.Effects and mechanism of plumbagin on the inflammatory response and oxidative stress in rats with AECOPD[J].ZHONGGUO YAOFANG,2025,36(18):2250-2255. DOI： 10.6039/j.issn.1001-0408.2025.18.06.

摘要

目的

基于Notch1/GATA3信号通路探究白花丹素对慢性阻塞性肺疾病急性加重期（AECOPD）大鼠炎症反应及氧化应激的影响及潜在机制。

方法

随机选择10只大鼠，作为对照组；另取65只大鼠，通过吸入香烟烟雾+气管滴注内毒素+鼻腔给菌的方式构建AECOPD模型，并将造模成功的50只大鼠随机分为AECOPD组、白花丹素低剂量组（10 mg/kg）、白花丹素高剂量组（50 mg/kg）、阳性对照组（地塞米松0.09 mg/kg）、白花丹素高剂量+Jagged1（Notch1激活剂）组（50 mg/kg+25 mg/kg），每组10只。各组大鼠灌胃和腹腔注射相应药液或生理盐水，每天1次，连续28 d。末次给药后，检测各组大鼠的肺功能指标（呼气流量峰值、0.3 s用力呼气容积与用力肺活量比值）、支气管肺泡灌洗液中的炎症细胞数（白细胞总数及淋巴细胞数、中性粒细胞数、巨噬细胞数）和炎症因子[白细胞介素6（IL-6）、IL-10、肿瘤坏死因子α（TNF-α）]水平以及肺组织中氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]含量，观察肺组织病理学变化并进行病理学评分，检测肺组织中黏蛋白5ac（Muc5ac）、Notch1、GATA3蛋白的表达情况。

结果

与对照组比较，AECOPD组大鼠肺泡壁结构严重受损，可见大量炎症细胞浸润，并伴有管壁增厚等病理学改变；肺功能指标、IL-10水平、SOD含量均显著降低；各炎症细胞数，IL-6、TNF-α水平，MDA含量，病理学评分，以及Muc5ac、Notch1、GATA3蛋白的表达均显著升高或上调（

＜0.05）；与AECOPD组比较，白花丹素各剂量组大鼠肺组织病理学变化均明显减轻，上述定量指标均显著改善，且高剂量组的改善更明显（

＜0.05）；Jagged1可显著逆转高剂量白花丹素对AECOPD大鼠肺损伤及相关指标的改善作用（

＜0.05）。

结论

白花丹素可抑制AECOPD大鼠肺部的炎症反应及氧化应激，减轻肺损伤，改善肺功能，上述作用可能与抑制Notch1/GATA3信号通路有关。

Abstract

OBJECTIVE

To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） based on Notch1/GATA3 signaling pathway.

METHODS

Ten rats were randomly selected as the control group； another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke， intratracheal administration of endotoxin， and nasal inoculation of bacteria. The 50 successfully modeled rats were randomly divided into the AECOPD group， plumbagin low-dose group （10 mg/kg）， plumbagin high-dose group （50 mg/kg）， positive control group （dexamethasone 0.09 mg/kg）， and high-dose plumbagin+Jagged1 （Notch1 activator） group （50 mg/kg+25 mg/kg）， with 10 rats in each group. Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline， once a day for 28 consecutive days. After the last administration， the lung function indicators （peak expiratory flow， the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity）， the number of inflammatory cells （white blood cells， lymphocytes， neutrophils， macrophages） in bronchoalveolar lavage fluid， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）] in lung tissue， and the contents of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in lung tissue were all determined in each group； the pathological changes of lung tissue and the pathological scores， as well as protein expressions of mucin 5ac （Muc5ac）， Notch1 and GATA3 in lung tissue were also detected.

RESULTS

Compared with the control group， the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure， with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall； their lung function indicators， IL-10 level， and SOD content were significantly decreased； while the number of various inflammatory cells， IL-6 and TNF-α levels， MDA cont

ent， pathological score， as well as protein expressions of Muc5ac， Notch1 and GATA3 were significantly increased or upregulated （

＜0.05）. Compared with the AECOPD group， the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated， and the above quantitative indicators were significantly improved， and the improvement was more obvious in the plumbagin high-dose group （

＜0.05）. Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats （

＜0.05）.

CONCLUSIONS

Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats， alleviate lung damage， and improve lung function. The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.

关键词

Keywords

references

邹曲，符丹丹，范腾阳，等 . 汉黄芩素对慢性阻塞性肺疾病模型大鼠气道炎症的影响及机制 [J ] . 中国药房， 2023 ， 34 （ 9 ）： 1060 - 1065 .

WANG X Q ， HAO Y J ， YIN Y J ， et al . Lianhua qingke preserves mucociliary clearance in rat with acute exacerbation of chronic obstructive pulmonary disease by maintai-ning ciliated cells proportion and protecting structural integrity and beat function of cilia [J ] . Int J Chron Obstruct Pulmon Dis ， 2024 ， 19 ： 403 - 418 .

张孝侠，吴友涛 . 金雀异黄酮对慢性阻塞性肺疾病急性加重期模型大鼠肺组织炎症反应的影响 [J ] . 中国临床药理学杂志， 2023 ， 39 （ 24 ）： 3633 - 3637 .

CHEN Z Y ， LIN Y M ， WU J H ， et al . Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD [J ] . BMC Pulm Med ， 2022 ， 22 （ 1 ）： 66 .

HE H D ， SUN S H ， XU W H ， et al . Network pharmaco-logy followed by experimental validation to explore the mechanism of stigmasterol in Sangbaipi decoction regula-ting PI3K/Akt signaling to alleviate acute exacerbation of chronic obstructive pulmonary disease [J ] . Int J Chron Obstruct Pulmon Dis ， 2024 ， 19 ： 1819 - 1834 .

RAHAMAN A ， ANJUM F ， KUMARI A ， et al . Deciphe-ring the binding mechanism of an anti-cancer phytoche-mical plumbagin with calf thymus DNA using biophysical and in silico techniques [J ] . Front Chem ， 2023 ， 11 ： 1248458 .

LIU Z J ， WEI J H ， SUN H B ， et al . Plumbagin ameliorates LPS-induced acute lung injury by regulating PI3K/Akt/mTOR and Keap1-Nrf2/HO-1 signalling pathways [J ] . J Cell Mol Med ， 2024 ， 28 （ 13 ）： e18386 .

黎阿果，蔡爱华，李浩甲，等 . PD-L1在肺部炎症性疾病中的研究进展 [J ] . 生理学报， 2024 ， 76 （ 2 ）： 346 - 352 .

杨霞，宁宗 . 巨噬细胞极化调控信号通路及M1/M2失衡在肺部炎症性疾病中作用的研究进展 [J ] . 山东医药， 2023 ， 63 （ 26 ）： 88 - 91 .

HUANG J J ， HU Y ， WANG Y X ， et al . Activation of Notch1-GATA3 pathway in asthma bronchial epithelial cells induced by acute PM 2.5 exposure and the potential protective role of microRNA-139-5p [J ] . J Asthma ， 2024 ， 61 （ 9 ）： 959 - 969 .

QIAO H ， WANG T Y ， YAN W ， et al . Synergistic suppression of human breast cancer cells by combination of plumbagin and zoledronic acid in vitro [J ] . Acta Pharmacol Sin ， 2015 ， 36 （ 9 ）： 1085 - 1098 .

高晓卫，刘迎迎，于潇，等 . 白花丹素介导sirt1-FOXO1通路对糖尿病肾病大鼠氧化应激损伤的影响 [J ] . 中国老年学杂志， 2024 ， 44 （ 1 ）： 170 - 174 .

廖小红，张毅靖，唐洪梅，等 . 苇茎汤对慢性阻塞性肺疾病急性加重期模型大鼠的改善作用及机制 [J ] . 中国药房， 2021 ， 32 （ 21 ）： 2593 - 2598 .

李伟艺，刘红松，高山瑛，等 . 基于Notch1/NF-κB信号通路探究补阳还五汤对脑缺血再灌注损伤的拮抗作用及其机制 [J ] . 西部中医药， 2022 ， 35 （ 11 ）： 16 - 21 .

杨善军，王玥，邢露茗，等 . 麦粒灸合补肺祛瘀方对肺纤维化大鼠肺功能和核因子κB信号通路的影响 [J ] . 世界中医药， 2022 ， 17 （ 24 ）： 3501 - 3505 .

DU X Q ， CHEN Y ， ZHANG R D ， et al . Effects of Qingjin huatan decoction on pulmonary function and inflammatory mediators in acute exacerbations of chronic obstructive pulmonary disease：a systematic review and meta-analysis [J ] . Front Pharmacol ， 2024 ， 15 ： 1466677 .

白春昀，翁稚颖，肖创，等 . 慢性阻塞性肺病相关炎症细胞及因子的研究进展 [J ] . 慢性病学杂志， 2019 ， 20 （ 1 ）： 42 - 46 .

王蓓，李皖豫，张珂，等 . 连翘提取物对肺炎链球菌感染慢性阻塞性肺疾病急性加重期大鼠的干预机制 [J ] . 中华医院感染学杂志， 2024 ， 34 （ 5 ）： 678 - 683 .

LI Z Z ， LI L ， LV X H ， et al . Ginseng saponin Rb 1 at-tenuates cigarette smoke exposure-induced inflammation，apoptosis and oxidative stress via activating Nrf2 and inhibiting NF-κB signaling pathways [J ] . Int J Chron Obstruct Pulmon Dis ， 2023 ， 18 ： 1883 - 1897 .

MEHDIZADEH S ， TAHERIAN M ， BAYATI P ， et al . Plumbagin attenuates bleomycin-induced lung fibrosis in mice [J ] . Allergy Asthma Clin Immunol ， 2022 ， 18 （ 1 ）： 93 .

CAI W X ， SHEN K ， JI P ， et al . The Notch pathway at-tenuates burn-induced acute lung injury in rats by repres-sing reactive oxygen species [J ] . Burns Trauma ， 2022 ， 10 ： tkac008 .

JIANG M ， CAI R ， WANG J ， et al . ILC2 cells promote Th2 cell differentiation in AECOPD through activated Notch-GATA3 signaling pathway [J ] . Front Immunol ， 2021 ， 12 ： 685400 .

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