目的 探讨黄连、干姜有效成分小檗碱、6-姜烯酚单独和联合应用对溃疡性结肠炎小鼠结肠上皮细胞Notch信号通路的影响。方法 50只昆明小鼠随机选取10只为对照组，其余40只采用2%葡聚糖硫酸钠（DSS）诱导溃疡性结肠炎模型。成模后随机分为模型组、小檗碱组、6-姜烯酚组、小檗碱＋6-姜烯酚组，ig给予相应药物，给药20 d后取结肠组织。免疫荧光法检测结肠上皮组织Hes-1、Math-1、MUC2、人类嗅素蛋白（olfm4）的表达，实时荧光定量PCR（qRT-PCR）、Western blotting法检测结肠上皮组织Notch-1、Hes-1、Math-1 mRNA和蛋白的表达。结果 与模型组比较，6-姜烯酚组、小檗碱组、小檗碱＋6-姜烯酚组小鼠结肠上皮组织Notch-1、Hes-1蛋白和mRNA表达水平显著降低，Math-1蛋白和mRNA表达水平显著升高，olfm4蛋白表达显著降低，MUC2蛋白表达水平显著升高；3组间比较，小檗碱＋6-姜烯酚组作用最明显。结论 6-姜烯酚、小檗碱均能够有效修复受损结肠黏膜，治疗溃疡性结肠炎，小檗碱和6-姜烯酚联合应用药效优于单独应用，其机制与抑制Notch通路的过度活化进而调节结肠上皮细胞增殖和分化相关。

Objective To investigate the effects of berberine and 6-shogaol on Notch signaling pathway in colonic epithelial cells of mice with ulcerative colitis. Methods A total of 50 Kunming mice were randomly selected as normal group, and the remaining 40 mice were treated with po 2% DSS to induce ulcerative colitis. The rats were randomly divided into model group, berberine group, 6-shogaol group, and berberine + 6-shogaol group. The corresponding drugs were given by ig administration. Colon tissues were taken after 20 d of administration. The protein expression of Hes-1, Math-1, MUC2, and olfm4 in colon epithelium was detected by immunofluorescence method, and the gene and protein expression of Notch-1, Hes-1, Math-1 in colon epithelium were detected by qRT-PCR and Western blotting. Results Compared with the model group, the protein and mRNA expression of Notch-1, Hes-1, and olfm4 in colon epithelium of mice in 6-shogaol group, berberine group, and berberine + 6-shogaol group were significantly decreased, while the expression of Math-1 and MUC2 were significantly increased. Among three groups, berberine + 6-shogaol group showed the best effect. Conclusion Both 6-shogaol and berberine can effectively repair damaged colonic mucosa and treat ulcerative colitis. The combined use of berberine and 6-shogaol is more effective than the single application. Its mechanism is related to inhibiting the over-activation of Notch pathway and regulating the proliferation and differentiation of colonic epithelium.

国家自然科学基金资助项目（81403320）；国家自然科学基金资助项目（81873233）；陕西省科技厅项目（2017SF-338）；陕西省科技厅项目（2018SF-284）；陕西中医药大学学科创新团队建设项目（2019-YL05）