哈萨克医经典名方吾孜德克治疗肠炎的物质基础及作用机制  

Material basis and mechanism of Kazakh classic prescription Wuzdekh in the treatment of enteritis

作　　者：贾丽萍 程波 史玉柱 何江 王雪 杨伟俊 JIA Liping;CHENG Bo;SHI Yuzhu;HE Jiang;WANG Xue;YANG Weijun(School of Food Science and Pharmacy,Xinjiang Agricultural University,Urumqi 830004,China;Key Laboratory of Xinjiang Uygur Medicine,Xinjiang Institute of Materia Medica,Urumqi 830004,China;LaboratoryⅡof Pharmacology,Xinjiang Institute of Materia Medica,Urumqi 830004,China)

机构地区：[1]新疆农业大学食品科学与药学学院,乌鲁木齐830004 [2]新疆维吾尔自治区药物研究所新疆维吾尔药重点实验室,乌鲁木齐830004 [3]新疆维吾尔自治区药物研究所药理Ⅱ实验室,乌鲁木齐830004

出　　处：《中国药房》2023年第13期1577-1583,共7页China Pharmacy

基　　金：新疆维吾尔自治区重大科技专项(No.2022A03003-3)。

摘　　要：目的探讨哈萨克医经典名方吾孜德克(WZDK)治疗肠炎的物质基础及潜在作用机制。方法利用液相色谱-串联质谱(LC-MS/MS)技术分析WZDK中的化学成分。通过网络药理学和分子对接技术筛选WZDK的主要化学成分并进行靶点预测,通过体内实验验证WZDK对急性肠炎的治疗作用及作用靶点。采用葡聚糖硫酸钠诱导构建小鼠急性肠炎模型,给药期间观察小鼠一般状况并计算疾病活动指数(DAI)评分,通过苏木素-伊红染色、实时荧光定量PCR验证各组小鼠肠道病理改变及核心靶点mRNA的表达。结果通过LC-MS/MS技术分析共得到316种化学成分;通过网络药理学分析,核心靶点主要包括白细胞介素1β(IL-1β)、蛋白激酶B1(AKT1)、肿瘤蛋白p53(TP53)、IL-6、肿瘤坏死因子(TNF)等;分子对接结果显示,白桦脂酸、lappadilactone、木香烃内酯、去氢木香内酯等化学成分与核心靶点结合稳定。体内实验结果显示,与模型组比较,高剂量(5.00 g/kg)WZDK能显著降低小鼠的DAI评分(P<0.05),改善其结肠组织炎症细胞浸润、黏膜组织损伤,显著下调其结肠组织中IL-6、TNF-α、IL-1β和TP53 mRNA的表达(P<0.05或P<0.01)。结论WZDK中的白桦脂酸、lappadilactone、木香烃内酯、去氢木香内酯等多种化学成分可能通过下调结肠组织中TNF-α、IL-6、IL-1β、TP53 mRNA表达,发挥改善肠道局部炎症因子失衡、修复结肠黏膜组织损伤的作用。OBJECTIVE To explore the material basis and potential mechanism of Kazakh classic prescription Wuzdekh(WZDK)in the treatment of enteritis.METHODS LC-MS/MS technology was used to analyze the chemical components in WZDK.Through network pharmacology and molecular docking technology,the main chemical components of WZDK were screened and the target was predicted;therapeutic effect and target of WZDK on acute enteritis were verified through in vivo experiments.The acute enteritis model of mice was induced by dextran sulfate sodium salt;the general condition of the mice was observed during administration and the disease activity index(DAI)score was calculated;pathological changes of the intestine and mRNA expression of core target were validated by HE staining and quantitative real-time PCR.RESULTS A total of 316 chemical components were obtained by LC-MS/MS.The core targets of network pharmacological analysis mainly included interleukin 1β(IL-1β),protein kinase B1(AKT1),tumor protein p53(TP53),IL-6,tumor necrosis factor(TNF)and so on.The results of molecular docking showed that chemical components such as mairin,lappadilactone,costunolide and dehydrocostus lactone were stable in binding to the core target.The results of in vivo experiment showed that,compared with model group,high dose(5.00 g/kg)of WZDK could significantly reduce the DAI score(P<0.05),improve inflammatory cell infiltration and mucosal tissue damage of colon tissue,and significantly down-regulated mRNA expressions of IL-6,TNF-α,IL-1βand TP53 in colon tissue(P<0.05 or P<0.01).CONCLUSIONS Chemical components of WZDK such as mairin,lappadilactone,costunolide and dehydrocostus lactone may play the role of improving the imbalance of local inflammatory factors in the intestine and repairing damage of colonic mucosal tissue by down-regulating mRNA expressions of TNF-α,IL-6,IL-1βand TP53 in colon tissue.

关 键 词：吾孜德克 哈萨克医 经典名方 网络药理学 分子对接 肠炎 

分 类 号：R965[医药卫生—药理学]