基于缓解化疗相关性腹泻作用的葛根芩连汤合煎和单煎等效性研究  

Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea

作　　者：李敏[1] 杨晓琴 成颜芬 吴淑洋 邹亮[2] 吴亿晗 章津铭[1] LI Min;YANG Xiao-qin;CHENG Yan-fen;WU Shu-yang;ZOU Liang;WU Yi-han;ZHANG Jin-ming(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,四川成都611137 [2]成都大学食品与生物工程学院,四川成都610106

出　　处：《中国中药杂志》2023年第11期2968-2980,共13页China Journal of Chinese Materia Medica

基　　金：2021年成都市科技人才创新创业项目(2021-RCO5-00020-CG);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-D-202209)。

摘　　要：对比研究葛根芩连汤(Gegen Qinlian Decoction,GQD)饮片单煎混合与传统复方合煎所得样品的化学概貌、组分含量、干膏率、药效等,为两者等效性研究提供依据,为临床中药配方颗粒应用的适宜性提供参考。采用相同的煎煮工艺分别制成GQD复方合煎和饮片单煎混合样品,基于UPLC-Q-Exactive Orbitrap MS技术对比分析两者化学概貌,同时采用高效液相色谱(HPLC)检测两者中9种指标性成分的含量差异,随后建立伊立替康所致迟发性腹泻小鼠模型,对比两者对化疗致腹泻的药效差异。基于UPLC-Q-Exactive Orbitrap MS的ESI+和ESI-模式分析,初步鉴定并归属GQD合煎和单煎混合样品中各59种化学成分,在成分种类上并没有明显的差异;9种指标性成分的含量结果表明,在合煎中的汉黄芩苷、黄芩苷含量相对较高,而在单煎中葛根素、大豆苷元、小檗碱、表小檗碱、黄芩素、甘草苷、大豆苷含量相对较高,进一步对GQD合煎和单煎中9种指标性成分进行统计学差异分析表明二者之间含量并未有显著性差异,且干膏得率结果表明GQD合煎与单煎样品中干膏得率也未有显著性差异;药效实验结果可得,与模型组相比,合煎与单煎样品组均能缓解小鼠体质量降低,降低腹泻指数,两者结肠组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、环氧化酶2(COX-2)、细胞间黏附分子-1(ICAM-1)、白细胞介素-10(IL-10)、丙二醛(MDA)、一氧化氮(NO)水平均降低,谷胱甘肽过氧化酶(GSH-Px)和超氧化物歧化酶(SOD)含量均显著上升;苏木素-伊红(HE)染色显示两者结肠组织细胞紧密排列,胞核清晰,未见明显差异。GQD复方合煎样品和单煎混合样品在化学成分的种类、9种指标性成分的含量、两者干膏得率与缓解化疗所致腹泻的药效上均未见明显差异,为中药复方合煎和单煎在传统汤剂和配方颗粒使用的灵活性和优劣性提供参考。This study compared the chemical profiles,component content,dry paste yield,and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD),aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application.The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD.Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS)was employed to compare the chemical profiles between the two groups.High-performance liquid chromatography(HPLC)was used to compare the content of nine characteristic components between the two groups.Then,a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea.The UPLC-QExactive Orbitrap MS in ESI+and ESI-modes identified 59 chemical components in the compound decoction and mixed single decoctions,which showed no obvious differences in component species.The content of baicalin and wogonoside was higher in the compound decoction,while that of puerarin,daidzein-8-C-apiosylglucoside,berberine,epiberberine,wogonin,glycyrrhizic acid,and daidzein was higher in the mixed single decoctions.Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions.The dry paste yield had no significant difference between the two groups.Compared with the model group,both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice.Both of them lowered the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),intercellular adhesion molecule-1(ICAM-1),interleukin-10(IL-10),malondialdehyde(MDA),and nitric oxide(NO)in the colon tissue.F

关 键 词：葛根芩连汤 配方颗粒 合煎 单煎 等效性 

分 类 号：R283.6[医药卫生—中药学]