益母草碱、黄精多糖、脱氧野尻霉素联合用药抗血栓和降血糖疗效的评价

Therapeutic effect evaluation of leonurine,polygonatum polysaccharide and deoxynojirimycin in combination on antithrombosis and hypoglycemia

目的通过建立和应用斑马鱼Ⅱ型糖尿病合并血栓模型,对益母草碱、黄精多糖、脱氧野尻霉素的联合用药在降血糖和抗血栓方面进行疗效评价。方法在链脲佐菌素建立斑马鱼Ⅱ型糖尿病模型的基础上,分别采用苯肼、花生四烯酸和普纳替尼建立血栓模型,设置对照组、模型组、二甲双胍+阿司匹林组、联合药高中低浓度组,进行药物干预后,观察尾静脉血栓形成情况;采用试剂盒测定各组幼鱼的组织糖含量;采用邻联茴香胺染色法对心脏红细胞进行定量分析,计算抑制血栓率;使用实时荧光定量聚合酶链反应检测相关血栓基因mRNA的表达。结果与模型组相比,联合用药能显著增加斑马鱼心脏红细胞染色强度、抑制血栓形成、下调血栓相关基因表达和降低组织糖含量。结论3种药物的联合使用可有效降低组织糖含量并具有抗血栓效果,在治疗Ⅱ型糖尿病和血栓药物开发方面具有巨大潜力。

Aim To evaluate the efficacy of the combination of leonurine(SCM),polygonatum polysaccharide(PSP)and deoxynojirimycin(DNJ)in hypoglycemic and antithrombotic aspects by establishing and using zebrafish type II diabetes combined with thrombosis model.Methods On the basis of the zebrafish type II diabetes model established by streptozotocin,phenylhydrazine(PH),arachidonic acid(AA)and ponatinib(PT)were used respectively to establish thrombosis models,which were divided into control group,model group,metformin+aspirin group,and the high,medium and low concentration groups of the combination drugs.After drug intervention in the experimental group,the thrombosis of tail vein was observed.Kit was used to determine the sugar content of juvenile fish tissues in each group.Quantitative analysis of cardiac erythrocytes by o-dianisidine staining method was used to calculate the inhibition rate of thrombus.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of related genes in zebrafish.Results Compared with the model group,the combined drug could significantly increase the staining intensity of erythrocytes in zebrafish hearts,inhibit thrombosis,down-regulate the expression of thrombosis-related genes,and reduce tissue glucose content.Conclusions The combined use of the three drugs can effectively reduce the tissue sugar content and have antithrombotic effect,which show great potential in the development of drugs for the treatment of type II diabetes and thrombosis.