基于反向分子对接技术研究桂枝汤调和营卫的潜在作用靶点  

Study on the Potential Targets of Guizhi Decoction Regulating Ying and Wei Based on Reverse Molecular Docking Technology

作　　者：施学丽[1] 郭超峰[2] 夏猛[3] 

机构地区：[1]广西中医药大学科技处,南宁530020 [2]广西中医药大学第一附属医院国家药物临床试验机构办公室,南宁530023 [3]广西中医药大学基础医学院,南宁530020

出　　处：《中国药房》2017年第25期3479-3483,共5页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81360514);广西壮族自治区卫生厅中医药普通课题(No.GZPT13-15);广西壮族自治区教育厅高校科研项目(No.YB2014180)

摘　　要：目的:基于经方的"方证相应"关系和反向分子对接技术研究桂枝汤调和营卫的潜在作用靶点。方法:通过文献检索获得桂枝汤相关的活性成分,采用Pharm Mapper Server对活性成分进行反向分子对接,依据对接分数排序发现桂枝汤的潜在受体,通过Auto Dock Vina进行正向分子对接试验考察配体与受体分子之间的亲和力。然后选取75只大鼠随机分为正常组、模型组和桂枝汤高、中、低剂量组(12、8、4 g/kg),每组15只,除正常组外的其余各组大鼠均复制营卫不和模型;成模后,各组大鼠每天ig给药1次,连续5 d;结束给药后检测大鼠脂肪组织和肌肉组织中11β-羟类固醇脱氢酶1型(11β-HSD1)表达水平。结果:对桂枝汤的活性成分进行反向分子对接发现11β-HSD1为频繁出现的受体,正向对接试验证实乌拉尔甘草皂苷b、甘草次酸、生胃酮等活性成分与11β-HSD1有较高的亲和力。动物实验结果显示,模型组大鼠脂肪组织和肌肉组织中11β-HSD1的表达水平较正常组大鼠升高(P<0.05);桂枝汤高剂量组大鼠脂肪组织和肌肉组织中11β-HSD1的表达水平较模型组降低(P<0.05)。结论:桂枝汤调和营卫的机制与11β-HSD1有一定的相关性;应用反向分子对接技术可以为"方证相应"关系的研究提供一条可行的技术途径。OBJECTIVE： To study the potential targets of Guizhi decoction regulating Ying and Wei based on ＂correspondence between formulation and syndrome＂ relationship and reverse molecular docking technology. METHODS： Active ingredients related to Guizhi decoction were obtained by literature retrievals, and PharmMapper Server was used for reverse molecular docking for ac- tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores, then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran- domly divided into normal group, model group, Guizhi decoction high-dose, medium-dose, low-dose groups （12, 8, 4 g/kg）, 15 in each group. Except for normal group, rats in other groups were induced for models with disharmony between Ying and Wei. Af- ter modeling, rats were intragastrically administrated once a day, for 5 d. After administration, 11β-HSD1 expression levels in adi- pose tissue and muscle tissue of rats were detected. RESULTS： Reverse molecular docking for active ingredients of Guizhi decoc- tion found that 11β-HSD1 was the frequent receptor, and positive docking test confirmed that uralsaponin b, glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed, compared with normal group, 11β- HSD1 expression levels in adipose tissue and muscle tissue in model group were increased （P〈0.05） ; and compared with model group, 11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased （P〈 0.05）. CONCLUSIONS： Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1, while the reverse molec- ular docking technology can provide a feasible technical way to study ＂correspondence between formulation and syndrome＂ relation- ship.

关 键 词：桂枝汤 反向分子对接 11β-羟类固醇脱氢酶1型 方证关系 

分 类 号：R285[医药卫生—中药学]