目的 研究蒙药特格希德格奇（糖尿乐）治疗糖尿病的药效及作用机制。方法 采用高脂饲料结合腹腔注射四氧嘧啶法建立2型糖尿病模型，给予二甲双胍和不同剂量的蒙药特格希德格奇（糖尿乐）干预后，测定小鼠空腹血糖（fasting blood glucose，FBG）、血清胰岛素（serum insulin，FINS）、总胆固醇（total cholesterol，TC）、甘油三酯（triglycerides，TG）、低密度脂蛋白（low-density lipoprotein，LDL-C）、高密度脂蛋白（high-density lipoprotein，HDL-C）水平，计算胰岛素抵抗指数（HOMA-IR）；通过苏木精-伊红（HE）观察小鼠胰腺组织病理学变化。通过中药系统药理学数据库分析平台（TCMSP）、化学专业数据库并结合文献查找蒙药特格希德格奇（糖尿乐）药物的化学成分，使用Swiss Target Prediction平台预测靶点；在人类孟德尔遗传数据库（OMIM）、DisGeNET数据库和GeneCards数据库中搜索糖尿病相关靶点，利用STRING数据库和Cytoscape 软件构建蛋白相互作用网络图；使用Metascape数据库对靶点进行基因本体（GO）注释和KEGG富集分析并利用Autodock软件进行分子对接。结果 蒙药特格希德格奇（糖尿乐）能够显著降低小鼠血糖、血清胰岛素、胰岛素抵抗指数、血脂水平，降低因ALX造模带来的胰岛组织坏死的范围，改善2型糖尿病小鼠。通过网络药理学搜集得到22个蒙药特格希德格奇（糖尿乐）潜在化学成分，525个药物靶点，13403个疾病靶点。经交集获得潜在靶点472个，核心靶点21个。KEGG通路富集分析涉及的信号通路有cAMP信号通路（cAMP signaling pathway）、cGMP-PKG信号通路（cGMP-PKG signaling pathway）、Th17细胞分化、MAPK信号通路（MAPK signaling pathway）、花生四烯酸代谢（Arachidonic acid metabolism）和脂肪细胞因子信号通路（Adipocytokine signaling pathway）等。分子对接结果显示，AKT1、EGFR、MAPK1、MAPK3、SRC与其相对应的活性成分均有较好的结合能力。结论 蒙药特格希德格奇（糖尿乐）确能够降低糖尿病药效其机制可能与调节cAMP信号通路、cGMP-PKG信号通路、Th17细胞分化、MAPK信号通路等通路的蛋白表达有关。

Objective To study the efficacy and mechanism of action of Mongolian medicine Tangniaole in the treatment of diabetes.Method A type 2 diabetes model was established by high-fat feed combined with intraperitoneal injection of tetraoxypyrimidine, and after the intervention of metformin and different doses of Mongolian medicine Tangniaole, fasting blood glucose (FBG), serum insulin (FINS), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were calculated in mice, and the insulin resistance index (HOMA-IR) was calculated. Histopathological changes in the pancreas of mice were observed by hematoxylin-eosin staining (HE).Through the traditional Chinese medicine system pharmacology database analysis platform (TCMSP), the chemical professional database and combined with the literature to find the chemical composition of the Mongolian medicine Tangniaole, also use the Swiss Target Prediction platform to predict the target;The targets related to diabetes were searched in human Mendelian genetic database (OMIM), DisGeNET database and GeneCards database, and the protein interaction network map was constructed using STRING database and Cytoscape software. Metascape database was used for gene ontology (GO) annotation and KEGG enrichment analysis, and Autodock software was used for molecular docking.Results Mongolian medicine Tangniaole could significantly decrease the blood glucose, serum insulin, insulin resistance index,lipid levels,reduced the area of pancreatic tissue necrosis caused by ALX modeling and improved type 2 diabetic mice. A total of 22 potential chemical constituents, 525 drug targets and 13403 disease targets were identified, 472 potential targets and 21 core targets were obtained through intersection. KEGG pathway enrichment analysis involved the cAMP signaling pathway, CTMP-PKG signaling pathway, Th17 cell differentiation, and MAPK signaling pathway signaling pathway, arachidonic acid metabolism and adipocytokine signaling pathway. Molecular docking showed that AKT1, EGFR, MAPK1, MAPK3 and SRC had good binding ability to their corresponding active components.Conclusions The mechanism of Mongolian drug Tangniaole can reduce the pharmacodynamic effect of diabetes, and its mechanism may be related to the protein expression of cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, MAPK signaling pathway and other pathways.

内蒙古自治区科技成果转化专项项目项目（AMCG201912）：蒙药特格希德格奇（糖尿乐）治疗糖尿的作用机制与临床疗效成果转化项目研究，负责人：马秀兰。