[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验...[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验,提高临床疗效。[方法]临床随诊在省内具有一定影响力的4位裘氏妇科传承人张萍青、吴燕平、王幸儿、张婷,规范采集和录入临床诊疗信息,建立名中医医案数据库,采用聚类分析、关联规则分析等技术,对各名中医的用药特点、辨证规律等进行数据分析挖掘,总结其共性规律。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)挖掘常用药对的活性成分及作用靶标,通过GeneCards数据库挖掘EMs的相关靶点,筛选出常用药对治疗EMs的靶标,利用Cytoscape软件构建活性成分-EMs靶标网络。利用生物学信息注释数据库进行基因本体(gene ontology,GO)生物过程与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)代谢通路富集分析,预测常用药对治疗EMs的分子机制。[结果]EMs临床常见证型包括瘀热互结证、肾虚血瘀证、气滞血瘀证。针对不同证型,4位医家辨证论治,同中存异,治疗瘀热互结证均以苦寒类的清热药及活血化瘀药为主,治疗肾虚血瘀证使用最多的药物均为补虚药及活血化瘀药,针对气滞血瘀证使用最多的药物均为理气药及活血化瘀药。其中丹参-赤芍药对是裘氏妇科治疗EMs的常用药对,通过TCMSP数据库共筛选出该药对的67种活性成分及78个治疗EMs的靶标,丹参-赤芍药对通过影响信号转导和转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,PKB1)、转录因子激活蛋白-1(activator protein-1,AP-1/JUN)、丝裂原活化蛋白激酶1(mitogen activated protein kinase 1,MAPK1)、核转录因子-κB p65(nuclear factor-κB p65,NF-κB p65/RELA)等关键靶点,调控磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinases B,PI3K-PKB)信号通路、白细胞介素-17(interleukin-17,IL-17)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等治疗EMs。[结论]4位裘氏妇科传承人治疗EMs,均以“肾虚”为本,“瘀”“热”互结为标,以苦寒、甘温之品补肾虚、化瘀血、清瘀热、行气滞,且善用药对。丹参-赤芍药对为裘氏妇科的常用药对,与裘笑梅先生清化逐瘀治疗EMs的学术思想相吻合。网络药理学揭示了该药对治疗EMs的分子机制,为进一步药效物质基础分析和分子机制研究提供了依据。展开更多
目的:建立HPLC法同时测定丹参-葛根药对中7种成分(葛根素、大豆苷、大豆苷元、丹酚酸B、隐丹参酮、丹参酮Ⅰ和丹参酮Ⅱ_(A))的含量,考察药对不同配比情况下7种成分溶出率的变化。方法:采用Diamonsil(Ⅱ)C_(18)ODS(250 mm×4.6 mm, 5...目的:建立HPLC法同时测定丹参-葛根药对中7种成分(葛根素、大豆苷、大豆苷元、丹酚酸B、隐丹参酮、丹参酮Ⅰ和丹参酮Ⅱ_(A))的含量,考察药对不同配比情况下7种成分溶出率的变化。方法:采用Diamonsil(Ⅱ)C_(18)ODS(250 mm×4.6 mm, 5μm)色谱柱,以乙腈-0.1%磷酸溶液为流动相,梯度洗脱;检测波长为250 nm;流速:1.0 ml·min^(-1);柱温:30℃;进样量:10μl。结果:7种成分在一定质量范围内与峰面积的线性关系良好(r≥0.999 3),平均加样回收率为98.3%~99.2%,RSD≤1.0%(n=6)。按不同比例配伍(7∶3、2∶1、1∶1、4∶3、3∶4、1∶2)的药对,7种成分溶出率均低于单味药材提取液,但配伍比例为1∶1时7种成分溶出率高于其他配伍比例。结论:所建立的含量测定方法简便、准确、重复性好。丹参-葛根药对1∶1配伍最有利于有效成分溶出。展开更多
Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Me...Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Methods:The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential targets of the pair were identified.The pharmacodynamics of the pair was analyzed using network pharmacology.The targets of IHD were identified by database screening.Using protein-protein interaction network,the interaction targets of Ginseng-Danshen on IHD were constructed.A"constituent-target-disease"interaction network was constructed using Cytoscape software,Gene Ontology(GO)term enrichment analysis and biological pathway enrichment analysis were carried out,and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.Results:Seventeen active constituents and 53 targets were identified from ginseng,53 active constituents and 61 targets were identified from Danshen,and 32 protein targets were shared by ginseng and Danshen.Twenty GO terms were analyzed,including cytokine receptor binding,cytokine activity,heme binding,and antioxidant activity.Sixty Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways were analyzed,including phosphatidylinositol 3-kinase-serine-threonine kinase(PI3 K-AKT)signaling pathway,p53 signaling pathway,interleukin 17 signaling pathway,tumor necrosis factor signaling pathway,and the advanced glycation end product(AGE)-the receptor for AGE(RAGE)signaling pathway in diabetic complications.Conclusion:The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody,inhibiting the production of peroxides,removing the endogenous oxygen free radicals,regulating the expression of inflammatory factors,reducing myocardial cell apoptosis and promoting vascular regeneration.展开更多
文摘[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验,提高临床疗效。[方法]临床随诊在省内具有一定影响力的4位裘氏妇科传承人张萍青、吴燕平、王幸儿、张婷,规范采集和录入临床诊疗信息,建立名中医医案数据库,采用聚类分析、关联规则分析等技术,对各名中医的用药特点、辨证规律等进行数据分析挖掘,总结其共性规律。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)挖掘常用药对的活性成分及作用靶标,通过GeneCards数据库挖掘EMs的相关靶点,筛选出常用药对治疗EMs的靶标,利用Cytoscape软件构建活性成分-EMs靶标网络。利用生物学信息注释数据库进行基因本体(gene ontology,GO)生物过程与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)代谢通路富集分析,预测常用药对治疗EMs的分子机制。[结果]EMs临床常见证型包括瘀热互结证、肾虚血瘀证、气滞血瘀证。针对不同证型,4位医家辨证论治,同中存异,治疗瘀热互结证均以苦寒类的清热药及活血化瘀药为主,治疗肾虚血瘀证使用最多的药物均为补虚药及活血化瘀药,针对气滞血瘀证使用最多的药物均为理气药及活血化瘀药。其中丹参-赤芍药对是裘氏妇科治疗EMs的常用药对,通过TCMSP数据库共筛选出该药对的67种活性成分及78个治疗EMs的靶标,丹参-赤芍药对通过影响信号转导和转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,PKB1)、转录因子激活蛋白-1(activator protein-1,AP-1/JUN)、丝裂原活化蛋白激酶1(mitogen activated protein kinase 1,MAPK1)、核转录因子-κB p65(nuclear factor-κB p65,NF-κB p65/RELA)等关键靶点,调控磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinases B,PI3K-PKB)信号通路、白细胞介素-17(interleukin-17,IL-17)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等治疗EMs。[结论]4位裘氏妇科传承人治疗EMs,均以“肾虚”为本,“瘀”“热”互结为标,以苦寒、甘温之品补肾虚、化瘀血、清瘀热、行气滞,且善用药对。丹参-赤芍药对为裘氏妇科的常用药对,与裘笑梅先生清化逐瘀治疗EMs的学术思想相吻合。网络药理学揭示了该药对治疗EMs的分子机制,为进一步药效物质基础分析和分子机制研究提供了依据。
基金Supported by the National Natural Science Foundation of China(No.81774145)Youth Program of National Natural Science Foundation of China(No.81503292)National Key Basic Research and Development Program(No.2015cb554406)。
文摘Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Methods:The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential targets of the pair were identified.The pharmacodynamics of the pair was analyzed using network pharmacology.The targets of IHD were identified by database screening.Using protein-protein interaction network,the interaction targets of Ginseng-Danshen on IHD were constructed.A"constituent-target-disease"interaction network was constructed using Cytoscape software,Gene Ontology(GO)term enrichment analysis and biological pathway enrichment analysis were carried out,and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.Results:Seventeen active constituents and 53 targets were identified from ginseng,53 active constituents and 61 targets were identified from Danshen,and 32 protein targets were shared by ginseng and Danshen.Twenty GO terms were analyzed,including cytokine receptor binding,cytokine activity,heme binding,and antioxidant activity.Sixty Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways were analyzed,including phosphatidylinositol 3-kinase-serine-threonine kinase(PI3 K-AKT)signaling pathway,p53 signaling pathway,interleukin 17 signaling pathway,tumor necrosis factor signaling pathway,and the advanced glycation end product(AGE)-the receptor for AGE(RAGE)signaling pathway in diabetic complications.Conclusion:The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody,inhibiting the production of peroxides,removing the endogenous oxygen free radicals,regulating the expression of inflammatory factors,reducing myocardial cell apoptosis and promoting vascular regeneration.