药物评价研究2024,Vol.47Issue(5) :1063-1070.DOI:10.7501/j.issn.1674-6376.2024.05.016

鼻咽清毒颗粒对鼻咽癌放射性口腔黏膜炎症损伤的保护作用及机制研究

Protective effect of Biyan Qingdu Granules on inflammatory injury of radioactive oral mucositis of nasopharyngeal carcinoma and its mechanism

王晓菲 王萌萌 徐旭 杨冰 石子叶 郭景玥 王丽 牛玉清 岳钰铭 田成旺 张铁军 李楚源 李鹏 杨洪军
药物评价研究2024,Vol.47Issue(5) :1063-1070.DOI:10.7501/j.issn.1674-6376.2024.05.016

鼻咽清毒颗粒对鼻咽癌放射性口腔黏膜炎症损伤的保护作用及机制研究

Protective effect of Biyan Qingdu Granules on inflammatory injury of radioactive oral mucositis of nasopharyngeal carcinoma and its mechanism

王晓菲 1王萌萌 1徐旭 2杨冰 2石子叶 1郭景玥 3王丽 1牛玉清 1岳钰铭 1田成旺 2张铁军 2李楚源 4李鹏 5杨洪军6
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作者信息

  • 1. 天津中医药大学研究生院,天津 301617;天津药物研究院天津市中药质量标志物重点实验室,天津 300301
  • 2. 天津药物研究院天津市中药质量标志物重点实验室,天津 300301
  • 3. 天津药物研究院天津市新药非临床评价技术工程中心,天津 300301
  • 4. 广州白云山和记黄埔中药有限公司,广东广州 510515
  • 5. 广州白云山和记黄埔中药有限公司,广东广州 510515;中国中医科学院,北京 100700
  • 6. 中国中医科学院,北京 100700
  • 折叠

摘要

目的 观察鼻咽清毒颗粒(BQG)对放疗引起大鼠口腔黏膜损伤的保护作用,并探讨其可能的作用机制.方法 采用FAT细胞皮下注射法,建立F344大鼠种植瘤模型.F344大鼠分为对照组、对照放射组、模型组、BQG低、中、高剂量(1、2、4g·kg-1)组.除对照组外,各组动物进行X线照射,放射剂量为10Gy·d-1,连续5d.BQG 3个剂量组于第1天造模后进行药物干预,每天ig给药1次,连续28d;其余3组给予等体积的蒸馏水.每日对各组大鼠进行一般观察,定期进行称重.末次给药后24h处死大鼠,采集各组大鼠口腔黏膜及血浆,酶联免疫吸附实验(ELISA)检测大鼠血浆中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因 α(TNF-α)水平;Western blotting检测口腔黏膜NF-κB p65、p-P65、MAPK、ERK、p-ERK等蛋白表达情况,并对其进行组织病理学检查.结果 BQG低、中、高剂量组均能提高大鼠体质量增长率;BQG各给药组能显著降低口轻黏膜组织中IL-6、IL-1β、TNF-α水平(P<0.05、0.01);与模型组比较,BQG各给药组MAPK蛋白表达显著降低,p-p65/p65,p-ERK/ERK比值显著降低(P<0.05、0.01).结论 BQG对放射性口腔黏膜炎具有修复作用,其可能通过调控NF-κB/MAPK/ERK信号通路,降低口腔黏膜炎症因子水平相关.

Abstract

Objective To observe the protective effect of Biyan Qingdu Granules(BQG)on radiotherapy-induced oral mucosal injury in rats and to explore its possible mechanism of action.Methods An F344 rat implantation tumor model was established by subcutaneous injection of FAT cells.F344 rats were divided into the control group,control radiation group,model group,and BQG low,medium,and high dose(1,2,and 4 g·kg-1)groups.Except for the control group,the animals in each group were subjected to X-ray irradiation at a radiation dose of 10 Gy·d-1 for five consecutive days.Three dose groups of BQG were subjected to pharmacological intervention after the first day of modeling,and the drug was administered by gavage once a day for 28 consecutive days.The remaining three groups were given equal volumes of distilled water.The rats in each group were subjected to general observation daily and weighed periodically.The rats were executed 24 h after the last administration.The oral mucosa and plasma of rats in each group were collected.The enzyme-linked immunosorbent assay(ELISA)detected interleukin-6(IL-6),interleukin 1β(IL-1β),and tumor necrosis factor α(TNF-α)in the plasma of rats.Western blotting detected the oral mucosa NF-κB p65,p-P65,MAPK,ERK,p-ERK,and other protein expression,and histopathological examination.Results The low,medium,and high dose groups of BQG could increase the body weight growth rate of rats;The administration groups of BQG could significantly reduce the levels of IL-6,IL-1 β,and TNF-α in the tissues of the oral light mucous membranes(P<0.05,0.01,respectively).Compared with the model group,the administration groups of BQG could significantly reduce the protein expression of MAPK,and the ratios ofp-p65/p65,p-ERK/ERK ratio were significantly reduced(P<0.05,0.01).Conclusion BQG have a therapeutic effect on radioactive oral mucositi,which may be related to reducing the level of oral mucosal inflammatory factors by regulating the NF-κB/MAPK/ERK signaling pathway.

关键词

放射性口腔黏膜炎/鼻咽清毒颗粒/鼻咽癌/口腔黏膜/MAPK/ERK/NF-κB

Key words

radiotherapy-induced oral mucositis/Biyan Qingdu Granules/nasopharyngeal cancer/oral mucosa/MAPK/ERK/NF-κB

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基金项目

广州市科技计划(20212210006)

出版年

2024
药物评价研究
天津药物研究院 中国药学会

药物评价研究

CSTPCD北大核心
影响因子:1.199
ISSN:1674-6376
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