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抑制HMG-Co A还原酶的他汀类药物与激动PPAR-α的贝特类药物联合应用相较于单纯应用能产生更好的降脂效果,但同时也会产生较强的不良反应。中药与HMG-Co A还原酶抑制剂合用治疗高血脂疗效稳定、毒副作用小,为药物联用提供了新的选择。该文利用药效团技术搜索中药化学成分,追溯其来源中药,确定潜在的具有PPAR-α激动活性的常用中药。由于现有中医经典中未涉及治疗高脂血症的相关用药方案以供参考,为确保所选中药的联合应用具有较高的安全性和有效性,该文选择世界传统药物专利数据库中已有临床验证的能与他汀类药物联合降脂之中药,并据此分析药效团命中结果中的相应药物,最终获得能作用于PPAR-α且能与他汀类药物联合使用的常用中药。其中,药效团模型以PPAR-α的8个配体-受体结合物为研究对象,利用DS程序中的Receptor-Ligand Pharmacophore Generation模块建立,并以Screen Library模块进行优化,获得最优子药效团。最优子药效团模型由2个氢键受体、3个疏水基团以及19个排除体积组成,辨识有效性指数N值2.82、综合评价指数CAI值1.84。采用该模型对TCMD数据库进行筛选,命中5 235种化学成分、1 193种来源天然动植物,最后确定常用中药62味。专利检索得到38味常用中药,与虚拟筛选结果进行比对,最终获得7味中药。
The combination of statins that inhibit HMG-Co A reductase with fibrates that agonize PPAR-α produces better lipid-lowering effects than simple applications, but also produces strong adverse effects. Chinese medicine and HMG-Co A reductase inhibitors combined treatment of hyperlipidemia with stable efficacy, small side effects, for drug combination provides a new choice. In this paper, pharmacophore technology was used to search the chemical constituents of traditional Chinese medicine. The traditional Chinese medicine with potential PPAR-α agonistic activity was identified by tracing the origin of traditional Chinese medicine. Due to the fact that the related prescriptions for treating hyperlipidemia are not included in the existing TCM classic for reference, in order to ensure the high safety and effectiveness of the combined application of the selected traditional Chinese medicines, Clinically validated drugs that can be combined with statins to reduce lipid levels. Based on this analysis, the corresponding drugs in the hits results were analyzed. Finally, the commonly used traditional Chinese medicines that can act on PPAR-α and can be used in combination with statins were obtained. Among them, the pharmacophore model is based on eight ligand-receptor conjugates of PPAR-α, and is established by using the Receptor-Ligand Pharmacophore Generation module in the DS program and optimized by the Screen Library module to obtain the optimal sub-drug Effective group. The optimal model of the proton pharmacophore consists of two hydrogen bond acceptors, three hydrophobic groups and 19 exclusion volumes. The validity index N is 2.82 and the comprehensive evaluation index CAI is 1.84. The TCMD database was screened by this model, with 5 235 chemical constituents and 1 193 native plants and plants, and finally 62 traditional Chinese herbs were identified. Patent search 38 commonly used traditional Chinese medicine, compared with the virtual screening results, and ultimately get seven kinds of Chinese medicine.