文献类型：期刊文献

中文题名：归芪白术方调节药物和胆汁酸代谢酶改善化疗性肠黏膜炎的作用机制研究

英文题名：Study on the Mechanism of Guiqi Baizhu Prescription in Improving Chemotherapy-induced Intestinal Mucositis by Regulating Drug and Bile Acid Metabolic Enzymes

作者：马晶[1,2,3,4];李亚玲[1,3,4];周昱岑[1,2,3,4];黄丹[1];李俊杰[1,3,4];司琦[1,3,4];瓦晓霞[1];刘永琦[1,3,4]

第一作者：马晶

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学中西医结合学院,甘肃兰州730000;[3]敦煌医学与转化教育部重点实验室,甘肃兰州730000;[4]甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2026

卷号：33

期号：2

起止页码：88

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：国家自然科学基金(82405224);甘肃省级人才项目(2025NQTD11);甘肃省中医药研究中心开放基金(ZYFY-2020-005);敦煌医学与转化教育部重点实验室开放基金(DHYX24-04)。

语种：中文

中文关键词：化疗性肠黏膜炎;归芪白术方;药物代谢酶;胆汁酸代谢酶;小鼠

外文关键词：chemotherapy-induced intestinal mucositis;Guiqi Baizhu Prescription;drug metabolism enzyme;bile acid metabolism enzyme;mice

摘要：目的通过转录组学等技术系统揭示归芪白术方调节药物代谢酶(DPYD、CYP3A4、GSTP1)、胆汁酸代谢酶(UGT1A1)及氧化应激改善5-氟尿嘧啶(5-FU)所致化疗性肠黏膜炎(CIM)的分子机制。方法将18只C57BL/6小鼠随机分为对照组(生理盐水5 mL/kg灌胃)、模型组(腹腔注射5-FU 50 mg/kg)、中药组(腹腔注射5-FU 50 mg/kg+归芪白术方17.94 g/kg灌胃),每组6只,每日干预1次,连续7 d。测量小鼠体质量并评估腹泻程度,HE染色观察回肠组织形态,免疫荧光染色检测肠屏障相关因子(ZO-1、Occludin)表达,转录组测序筛选差异表达基因,通过RT-PCR和Western blot验证差异基因mRNA和蛋白表达。结果与对照组比较,模型组小鼠体质量减少,腹泻评分增加(P<0.01),回肠组织水肿,黏膜上皮细胞脱落,绒毛长度缩短,隐窝深度减少(P<0.01),回肠组织Occludin、ZO-1表达降低,IL-1β、TNF-α表达升高(P<0.01)。与模型组比较,中药组小鼠体质量增加,腹泻评分降低(P<0.05),回肠组织水肿减轻,绒毛长度延长,隐窝深度增加(P<0.01),回肠组织Occludin、ZO-1表达升高,IL-1β、TNF-α表达降低(P<0.05,P<0.01)。转录组测序筛选出1091个差异表达基因,GO和KEGG通路富集分析表明药物代谢与胆汁酸代谢通路是其核心调控机制。TOP20的KEGG通路相关基因主要来自CYP、GST、UGT基因家族。RT-PCR验证结果显示,与对照组比较,模型组小分子代谢酶(DPYD、GSTP1、CYP3A4)、胆汁酸代谢酶(UGT1A1、UGT1A9)及胆汁酸受体(FXR、TGR5)表达均显著下调,中药组可逆转上述变化。Western blot验证结果显示,中药组可逆转模型组DPYD、CYP3A4、GSTP1、UGT1A1、FXR、TGR5蛋白表达下调,还可上调抗氧化酶HO-1、NQO1蛋白表达。结论归芪白术方可能通过调节5-FU药物代谢和胆汁酸代谢等关键酶及氧化应激改善CIM肠道炎症和屏障破坏。
Objective To systematically reveal the molecular mechanism of Guiqi Baizhu Prescription in improving chemotherapy-induced intestinal mucositis(CIM)induced by 5-fluorouracil(5-FU)by regulating drug metabolizing enzymes(DPYD,CYP3A4,GSTP1),bile acid metabolizing enzymes(UGT1A1)and oxidative stress.Methods Totally 18 C57BL/6 mice were randomly divided into control group(normal saline 5 mL/kg by gavage),model group(intraperitoneal injection of 5-FU 50 mg/kg)and TCM group(intraperitoneal injection of 5-FU 50 mg/kg+Guiqi Baizhu Prescription 17.94 g/kg by gavage),with 6 mice in each group.The mice were intervened once a day for 7 days.The body mass of mice was measured and the degree of diarrhea was evaluated,the morphology of ileum was observed by HE staining,the expression of intestinal barrier related factors(ZO-1,Occludin)was detected by immunofluorescence staining,the differentially expressed genes were screened by transcriptome sequencing.The mRNA and protein expression of differentially expressed genes were verified by RT-PCR and Western blot.Results Compared with the control group,the body mass of mice in the model group decreased,the diarrhea score increased(P<0.01),ileum edema,mucosal epithelial cells shed,villus length shortened,crypt depth decreased(P<0.01),the expressions of Occludin and ZO-1 in ileum decreased,and the expressions of IL-1β and TNF-α increased(P<0.01).Compared with the model group,the body mass of mice inTCM group increased,the diarrhea score decreased(P<0.05),the edema of ileum tissue decreased,the length of villi prolonged,the depth of crypt increased(P<0.01),the expressions of Occludin and ZO-1 in ileum tissue increased,and the expressions of IL-1β and TNF-α decreased(P<0.05,P<0.01).1091 differentially expressed genes were screened by transcriptome sequencing.GO and KEGG enrichment analysis showed that drug metabolism and bile acid metabolism pathway were the core regulatory mechanisms.The KEGG pathway related genes of TOP20 were mainly from CYP,GST and UGT gene families.RT-PCR results showed that compared with the control group,the expressions of small molecular metabolic enzymes(DPYD,GSTP1,CYP3A4),bile acid metabolic enzymes(UGT1A1,UGT1A9)and bile acid receptors(FXR,TGR5)in the model group significantly decreased,and the TCM group could reverse the above changes.Western blot analysis showed that the TCM group can reverse the downregulation of DPYD,CYP3A4,GSTP1,UGT1A1,FXR and TGR5 protein expression,and also up-regulate the expressions of antioxidant enzymes HO-1 and NQO1 protein.Conclusion Guiqi Baizhu Prescription may improve intestinal inflammation and barrier damage in CIM by regulating key enzymes such as 5-FU drug metabolism and bile acid metabolism and oxidative stress.