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

作　　者：宋立朝 程念 邓逸菲 周文 刘端勇[2] 赵海梅[2] 李燕珍 SONG Lizhao;CHENG Nian;DENG Yifei;ZHOU Wen;LIU Duanyong;ZHAO Haimei;LI Yanzhen(Graduate School,Jiangxi University of Chinese Medicine,Nanchang 330004;Fangzheng Research Center,Jiangxi University of Chinese Medicine,Nanchang 330004;Scientific Research Office,Nanchang Medical College,Nanchang 330052;College of Clinical Medicine,Nanchang Medical College,Nanchang 330052)

机构地区：[1]江西中医药大学研究生院,南昌330004 [2]江西中医药大学方证研究中心,南昌330004 [3]南昌医学院科研处,南昌330052 [4]南昌医学院临床医学院,南昌330052

出　　处：《中药药理与临床》2025年第2期16-20,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:82060799);江西省教育厅科学技术项目(编号:GJJ218916);江西中医药大学博士科研启动基金课题(编号:20224BSZR010);江西省研究生创新专项资金项目(编号:YC2023-S749)。

摘　　要：目的:验证四神丸干预Numb/Notch信号通路活化,探究四神丸治疗溃疡性结肠炎的可能作用机制。方法:将40只雄性BALB/c小鼠分为正常对照组、四神丸正常给药组、模型对照组、四神丸2.5 g/kg组,每组10只。采用葡聚糖硫酸钠(DSS)诱导小鼠溃疡性结肠炎,四神丸正常给药组及四神丸2.5 g/kg组每天给予四神丸混悬液灌胃干预,采用体质量、结肠长度、结肠质量、结肠质量指数、疾病活动指数(DAI)、病理损伤评分等评价其疗效;采用Western blot法检测结肠组织Notch信号通路相关蛋白如Notch受体3(Notch3)、锯齿典型Notch配体1(Jagged1)、德尔塔样配体1(DLL1)、德尔塔样配体4(DLL4)、RNA结合蛋白(MSI2)、主导控制样蛋白1(MAML1)以及衔接蛋白(Numb)的表达;采用RT-qPCR法检测Notch受体1(Notch1)、Notch3、Numb mRNA的表达;并用免疫组化标记结肠组织中Notch3蛋白的表达。结果:与正常对照组相比,模型对照组小鼠体质量明显降低(P<0.05或P<0.01),DAI评分显著升高(P<0.01),病理损伤评分显著升高(P<0.01),Notch1 mRNA表达显著上调(P<0.01),Notch3、Jagged1、DLL1、DLL4、MSI2及MAML1的蛋白表达均明显上调(P<0.05或P<0.01),Numb mRNA及蛋白表达明显下调(P<0.05或P<0.01);与模型对照组相比,四神丸2.5 g/kg组小鼠体质量明显升高(P<0.05或P<0.01),DAI评分显著降低(P<0.01),病理损伤评分显著降低(P<0.01),Notch1 mRNA表达显著下调(P<0.01),Notch3、Jagged1、DLL1、DLL4、MSI2及MAML1的蛋白表达均明显下调(P<0.05或P<0.01),Numb mRNA及蛋白表达明显上调(P<0.05或P<0.01)。结论:四神丸有效减轻DSS诱导的小鼠溃疡性结肠炎,可能与抑制Numb/Notch信号过度活化有关。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 reduc

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1 

分 类 号：R285.5[医药卫生—中药学]