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

作　　者：王晓菲 王萌萌 徐旭[2] 杨冰 石子叶 郭景玥[3] 王丽 牛玉清 岳钰铭 田成旺[2] 张铁军[2] 李楚源[4] 李鹏 杨洪军[5] WANG Xiaofei;WANG Mengmeng;XU Xu;YANG Bing;SHI Ziye;GUO Jingyue;WANG Li;NIU Yuqing;YUE Yuming;TIAN Chengwang;ZHANG Tiejun;LI Chuyuan;LI Peng;YANG Hongjun(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300301,China;Tianjin Engineering Center for Non-Clinical Evaluation of New Drugs,Tianjin Institute of Pharmaceutical Research,Tianjin 300301,China;Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co.,Ltd.,Guangzhou 510515,China;China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]天津中医药大学研究生院,天津301617 [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]中国中医科学院,北京100700

出　　处：《药物评价研究》2024年第5期1063-1070,共8页Drug Evaluation Research

基　　金：广州市科技计划项目(20212210006)。

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、4 g·kg^(−1))组。除对照组外,各组动物进行X线照射,放射剂量为10 Gy·d^(−1),连续5 d。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28 d;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24 h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。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 Xray 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 factorα(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-1β,and TNF-αin 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 of p-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 

分 类 号：R285.5[医药卫生—中药学]