中药药理与临床2025，Vol.41Issue(2)：16-20,5.
四神丸对结肠炎小鼠结肠粘膜Numb/Notch信号的调节作用
Sishen Pills(四神丸)in Regulation of Numb/Notch Signals in Colonic Mucosa of Mice with Colitis
摘要
Abstract
Objective:To validate the intervention of Sishen Pills(四神丸)in the activation of the Numb/Notch signaling pathway and to explore the possible mechanism of Sishen Pills in the treatment of ulcerative colitis(UC).Methods:Forty male BALB/c mice were divided into a normal control group,a normal Sishen Pills group,a model control group,and Sishen Pills 2.5 g/kg group,with 10 mice in each group.UC was induced in the mice using dextran sulfate sodium(DSS).The normal Sishen Pills group and the Sishen Pills 2.5 g/kg group were ad-ministered Sishen Pills suspension daily via gavage.The efficacy of treatment was assessed using body weight,colon length,colon weight,co-lon weight index,disease activity index(DAI),and pathological damage score.Protein expression levels related to the Notch signaling path-way,including Notch receptor 3(Notch3),Jagged canonical Notch ligand 1(Jagged1),delta-like ligand 1(DLL1),delta-like ligand 4(DLL4),RNA-binding protein Musashi2(MSI2),Mastermind-like 1(MAML1),and bridging protein Numb,were detected by Western blot.Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression of Notch receptor 1(Notch1),Notch3,and Numb.Immunohistochemistry(IHC)was used to label Notch3 protein expression in colon tissues.Results:Com-pared with the normal control group,the model control group showed significantly decreased body weight(P<0.05 or P<0.01),significantly increased DAI scores(P<0.01),and significantly elevated pathological damage scores(P<0.01).The expression level of Notch1 mRNA was significantly upregulated(P<0.01),and the protein expression levels of Notch3,Jagged1,DLL1,DLL4,MSI2,and MAML1 were also sig-nificantly upregulated(P<0.05 or P<0.01).In contrast,Numb mRNA and its protein expression levels were significantly downregulated(P<0.05 or P<0.01).Compared with the model control group,the Sishen Pills 2.5 g/kg group showed significantly increased body weight(P<0.05 or P<0.01),significantly decreased DAI scores(P<0.01),and significantly reduced pathological damage(P<0.01).The expres-sion level of Notch1 mRNA was significantly downregulated(P<0.01),and the protein expression levels of Notch3,Jagged1,DLL1,DLL4,MSI2,and MAML1 were significantly downregulated(P<0.05 or P<0.01),while Numb mRNA and its protein expression levels were signifi-cantly upregulated(P<0.05 or P<0.01).Conclusion:Sishen Pills effectively alleviate DSS-induced UC in mice,possibly by inhibiting the overactivation of the Numb/Notch signaling pathway.关键词
四神丸/溃疡性结肠炎/衔接蛋白/Notch信号通路/锯齿典型Notch配体 1/德尔塔样配体 1Key words
Sishen Pills(四神丸)/Ulcerative colitis/Numb/Notch signaling pathway/Jagged1/DLL1引用本文复制引用
宋立朝,程念,邓逸菲,周文,刘端勇,赵海梅,李燕珍..四神丸对结肠炎小鼠结肠粘膜Numb/Notch信号的调节作用[J].中药药理与临床,2025,41(2):16-20,5.基金项目
国家自然科学基金项目(编号:82060799) （编号:82060799）
江西省教育厅科学技术项目(编号:GJJ218916) （编号:GJJ218916）
江西中医药大学博士科研启动基金课题(编号:20224BSZR010) （编号:20224BSZR010）
江西省研究生创新专项资金项目(编号:YC2023-S749). （编号:YC2023-S749）
