用于口服固体制剂药效学研究的大鼠DMH/DSS炎症相关结直肠癌模型的建立  

Establishment of DMH/DSS inflammation-related colorectal cancer rat model for pharmacodynamic research of oral solid preparations

作　　者：余玲 刘葭[1] 郝逗逗 郭子右 刘玉娟 吴清[1] YU Ling;LIU Jia;HAO Dou-dou;GUO Zi-you;LIU Yu-juan;WU Qing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中南药学》2021年第2期208-215,共8页Central South Pharmacy

基　　金：国家自然科学基金资助项目(No.81773915)。

摘　　要：目的建立大鼠1,2-二甲肼(DMH)/葡聚糖硫酸钠(DSS)炎症相关结直肠癌模型,为口服固体制剂用于炎症相关结直肠癌的药效学研究提供模型基础。方法采用DMH/DSS复合法诱导Wistar大鼠建立炎症相关结直肠癌模型,通过对宏观指标的观察和组织病理学检查,判断不同造模方案的造模效果,确定最佳造模方案,并以当归汤提取物及其微丸制剂给药进行药效学评价,通过宏观指标、组织病理学检查、炎症因子指标等,验证造模方法的可行性。结果确定的最佳造模方案为第1周的第1日开始饮用2%DSS 7 d,自由饮水7 d,4个循环,共8周,且第一周开始腹腔注射40 mg·kg-1 DMH,每周注射一次,共注射8次,并于第14周解剖取材,模型组大鼠结直肠表现为早期腺癌。与模型组相比,当归汤提取物、当归汤提取物微丸干预后能够减少大鼠结直肠肿瘤个数和体积,降低肿瘤发生率,降低炎症因子和铁调素水平,延缓癌症发展程度,且微丸给药组效果优于提取物组。结论以40 mg·kg-1 DMH腹腔注射结合2%DSS自由饮用复合诱导法,可以成功复制炎症相关结直肠癌大鼠模型,该方法简单易行,可用于口服固体制剂的药效学研究。Objective To establish rat model for the pharmacodynamic research of oral solid preparations for DMH/DSS inflammation-related colorectal cancer.Methods The DMH/DSS compound method was used to induce Wistar rats to establish the inflammation-related colorectal cancer model.Through macroscopic indicators and histopathological examination,the effect of different modelling schemes was evaluated,and the best modelling scheme was determined.Angelica sinensis decoction extract and its pellets were administered for pharmacodynamic evaluation,and the feasibility of the modeling method was verified through macroscopic indicators,histopathological examinations,and inflammatory factor indicators.Results The best modelling plan was:drinking 2%DSS for 7 days in the first week,free water drinking for 7 days,for 4 cycles,a total of 8 weeks;intraperitoneal injection of 40 mg·kg-1 DMH in the first week,injection weekly,for a total of 8 weeks;anatomy and collection at the 14th week.The colorectal rats in the model group showed early adenocarcinoma.After the intervention of Angelica sinensis decoction extract and its pellets,the number and volume of rat colorectal tumors,the incidence of tumors,the levels of inflammatory factors and hepcidin were reduced,and the development of cancer was delayed.The effect of the pellet administration group was better than that of the extract group.Conclusion Intraperitoneal injection of 40 mg·kg-1 DMH combined with 2%DSS free-drinking compound induction can successfully replicate the inflammation-related colorectal cancer rat model.This method is simple and easy to implement and can be used for the pharmacodynamic research of oral solid preparations.

关 键 词：1 2-二甲肼 葡聚糖硫酸钠 炎症相关结直肠癌 大鼠模型 口服固体制剂 

分 类 号：T35.3[一般工业技术]