摘要
目的:基于分子对接技术探讨还涎方抑制溃疡性结肠炎(UC)癌前病变的作用机制。方法:选取60只BALB/C小鼠,随机分为空白组、模型组、还涎方组、美沙拉嗪组、康复新液组,每组12只。使用氧化偶氮甲烷和葡聚糖硫酸钠诱导建立UC癌前病变模型,采用保留灌肠法治疗UC。观察小鼠便隐血情况,计算疾病活动指数(DAI)评分、结肠炎症反应评分;利用系统药理学分子高通量技术筛选获得关键靶点,进行病理HE染色及Western blot验证,利用分子对接技术分析还涎方中主要成分与关键靶点的结合能力。结果:与模型组比较,还涎方可显著缓解UC癌前病变小鼠便隐血症状,降低DAI评分及结肠黏膜损伤(P<0.01)。高通量筛选得出关键靶点p53、cox-2、bcl-2;与空白组比较,模型组p53、cox-2和bcl-2蛋白表达水平显著升高(P<0.01);与模型组比较,还涎方组p53、cox-2和bcl-2蛋白表达水平显著降低(P<0.01)。p53、cox-2和bcl-2与还涎方中主要成分进行分子对接,亲和力水平cox-2>p53>bcl-2。结论:还涎方可通过干预cox-2、p53、bcl-2靶点抑制UC癌前病变的发生。
Objective:To explore the mechanism of Huanxian Formula(HXF)in inhibiting precancerous lesions of ulcerative colitis(UC)based on molecular docking.Methods:Sixty BALB/C mice were randomly divided into blank group,model group,HXF group,mesalazine group and Kangfuxin liquid group,12 mice in each group.AOM+DSS was used to induce the establishment of a UC precancerous lesion model,and retention enema was used to treat UC.The mice condition of fecal occult blood was observed,the disease activity indexes(DAI)scores and colonic inflammatory reaction scores were caculated.The key targets were screened and validated by pathological HE staining and Western blot,and the binding ability of the main components of the HXF to the key targets was analyzed by molecular docking technique.Results:Compared with the model group,the HXF could significantly alleviate the symptoms of fecal occult blood,reduce the DAI score and colonic mucosal damage in UC precancerous mice(P<0.01).High-throughput screening identified key targets p53,cox-2 and bcl-2;p53,cox-2 and bcl-2 protein expression levels in the model group were significantly higher than those in the control group(P<0.01),and which in the HXF group significantly lower than those in the model group(P<0.01).The molecular docking of p53,cox-2,bcl-2 with the main components in the HXF,the affinity level was cox-2>p53>bcl-2.Conclusion:HXF could inhibit the occurrence of UC precancerous lesions by interfering with cox-2,p53 and bcl-2 targets.
作者
孙姮
闫珺
李雨
庞雪莹
王鹏
张俐佳
刘松江
SUN Heng;YAN Jun;LI Yu;PANG Xue-ying;WANG Peng;ZHANG Li-jia;LIU Song-jiang(Heilongjiang University of Chinese Medicine,Harbin 150040,China;First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第5期2826-2830,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
黑龙江省省属本科高校中央支持地方高校改革发展高水平人才项目(No.2020G S P07)
哈尔滨市科技局科技创新人才基金青年后备人才(B类)项目(No.H2017054)
黑龙江省博士后面上资助项目(No.LBH-Z18251)。
