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补中益气汤调控黏蛋白-胆汁酸-菌群代谢防治炎癌转化研究
董国强,刘韦鋆,张兴洲,张楠
天津医科大学附属南开医院天津 300100;天津市中西医结合急腹症研究所天津 300100;天津市急腹症器官损伤与中西医修复重点实验室 天津 300100
摘要:
目的:探讨补中益气汤调控肠道黏蛋白-胆汁酸-菌群代谢防治肠道炎癌转化的机制。方法:选取Wistar大鼠,构建结肠炎癌转化模型,进行动物实验和靶向代谢物检测。采用“solvent-shift”法和细胞共培养模型,设计过饱和稳定性和转运实验。采用PCR、ELISA及HPLC检测相关指标。结果:与正常组相比,模型组大鼠一般状态恶化,且死亡率、成瘤率、炎性因子或黏蛋白表达显著升高,而补中益气汤组上述指标均显著改善(P <0.05)。模型组代谢轮廓紊乱,补中益气汤组可部分恢复。筛选出4个共有差异代谢物和5条代谢路径。关键代谢路径为胆汁酸生物合成和维生素K代谢。黏蛋白显著增加空腹状态模拟肠液中胆固醇和初级胆汁酸的激增后时间(TSS)及曲线下面积(AUC)(P <0.05),且黏液分泌细胞单层对其流出增量(FE)显著增强(P <0.05)。结论:在炎性肠病状态下,炎性因子诱导的黏蛋白2(MUC2)高表达促进胆固醇吸收并维持初级胆汁酸过饱和,进而提升其菌群代谢转化为次级胆汁酸水平,通过影响菌群功能与短链脂肪酸代谢促进炎癌转化。补中益气汤抑制肠道黏蛋白-胆汁酸-菌群代谢,防治肠道炎癌转化。
关键词:  补中益气汤  黏蛋白  胆汁酸  肠道菌群代谢  炎癌转化
DOI:10.3969/j.issn.1007-6948.2026.03.026
投稿时间:2025-10-02
基金项目:天津市卫生健康委中医中西医结合科研课题(2023096);天津市医学重点学科建设项目(TJYXZDXK-3-028C)
Studies on the mechanism of Buzhong Yiqi decoction in regulating mucin-bile acid-microbiota metabolism for preventing inflammatory-cancerous transformation
DONG Guo-qiang,LIU Wei-jun,ZHANG Xing-zhou
Abstract:
Objective To investigate the mechanism of Buzhong Yiqi decoction in preventing intestinal inflammation-cancer transformation by regulating the gut mucin-bile acid-microbiota metabolism. Methods A colitis-associated cancer transformation model was established to conduct animal experiments and targeted metabolite analyses. The "solvent-shift" method and a co-culture cell model were utilized to design supersaturation stability and cellular transport assays. PCR, ELISA, and HPLC were applied to detect relevant biomarkers. Results Compared with the normal group, the model group showed deteriorated general status, with significantly increased mortality, tumor incidence, inflammatory factors, and mucin expression, whereas Buzhong Yiqi decoction administration significantly improved these indicators (P <0.05). The metabolic profile was disturbed in the model group and partially restored by Buzhong Yiqi decoction. Four intersection differential metabolites and five metabolic pathways were identified. Key pathways included bile acid biosynthesis and vitamin K metabolism. Mucin significantly increased the TSS or AUC of cholesterol and primary bile acids in FaSSIF (P <0.05), and the FE across mucus-secreting cell monolayers was significantly enhanced (P <0.05). Conclusion Under inflammatory bowel disease conditions, inflammatory factor-induced MUC2 overexpression promotes cholesterol absorption and maintains primary bile acid supersaturation, thereby elevating their microbial conversion to secondary bile acids. This process may promote inflammation-cancer transformation by affecting microbiota function and short-chain fatty acid metabolism. Buzhong Yiqi decoction inhibits the intestinal mucin-bile acid-microbiota metabolism, preventing and treating intestinal inflammation-cancer transformation.
Key words:  Buzhong Yiqi decoction  mucin  bile acids  gut microbiota metabolism  inflammation-cancer transformation

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