目的研究敲减PTGS2对成纤维细胞全基因组表达谱的影响,在基因水平上探索防治瘢痕疙瘩的新途径。方法运用RNAi干扰正常皮肤成纤维细胞前列腺素内过氧化物合酶2(PTGS2)基因的表达,利用real time RT-PCR验证siRNA沉默效果;应用全基因组芯...目的研究敲减PTGS2对成纤维细胞全基因组表达谱的影响,在基因水平上探索防治瘢痕疙瘩的新途径。方法运用RNAi干扰正常皮肤成纤维细胞前列腺素内过氧化物合酶2(PTGS2)基因的表达,利用real time RT-PCR验证siRNA沉默效果;应用全基因组芯片检测基因表达谱变化。结果成纤维细胞的PTGS2基因经siRNA干扰后,其mRNA表达水平明显下调;全基因组芯片表达谱检测到的差异表达基因,按1.5倍差异共189个(115个上调,74个下调),按2倍差异共14个(9个上调,5个下调);基因表达谱的变化与瘢痕疙瘩基因表达谱的变化相吻合,可能促使正常皮肤成纤维细胞向瘢痕疙瘩方向进展。结论检测到与PTGS2基因相关的、在瘢痕疙瘩形成中可能共同发挥作用的相关基因,证明PTGS2与瘢痕疙瘩的发病机制有着密切的关系,为治疗瘢痕疙瘩提供了一个潜在的候选靶点。展开更多
Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal ex...Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.展开更多
[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analys...[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用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)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。展开更多
目的:研究隔药灸治疗子宫内膜异位症大鼠模型的疗效及机制。方法:构建子宫内膜异位症大鼠模型并随机分为治疗组、孕三烯酮组、模型组和假手术组。经治疗后,采集大鼠病灶标本,观察隔药灸对大鼠异位子宫内膜体积的抑制作用,计算抑制率;R...目的:研究隔药灸治疗子宫内膜异位症大鼠模型的疗效及机制。方法:构建子宫内膜异位症大鼠模型并随机分为治疗组、孕三烯酮组、模型组和假手术组。经治疗后,采集大鼠病灶标本,观察隔药灸对大鼠异位子宫内膜体积的抑制作用,计算抑制率;RT-PCR法检测各组大鼠异位子宫内膜的KDR和PTGS2 m RNA表达。结果:经隔药灸治疗后大鼠模型的异位子宫内膜体积较模型组明显缩小;治疗组大鼠模型的异位子宫内膜PTGS2和KDRm RNA表达均明显低于模型组。结论:隔药灸能明显抑制大鼠模型异位子宫内膜的发展,并且这种治疗作用可能与抑制KDR和PTGS2表达,从而调控异位子宫内膜血管生成有关。展开更多
文摘目的研究敲减PTGS2对成纤维细胞全基因组表达谱的影响,在基因水平上探索防治瘢痕疙瘩的新途径。方法运用RNAi干扰正常皮肤成纤维细胞前列腺素内过氧化物合酶2(PTGS2)基因的表达,利用real time RT-PCR验证siRNA沉默效果;应用全基因组芯片检测基因表达谱变化。结果成纤维细胞的PTGS2基因经siRNA干扰后,其mRNA表达水平明显下调;全基因组芯片表达谱检测到的差异表达基因,按1.5倍差异共189个(115个上调,74个下调),按2倍差异共14个(9个上调,5个下调);基因表达谱的变化与瘢痕疙瘩基因表达谱的变化相吻合,可能促使正常皮肤成纤维细胞向瘢痕疙瘩方向进展。结论检测到与PTGS2基因相关的、在瘢痕疙瘩形成中可能共同发挥作用的相关基因,证明PTGS2与瘢痕疙瘩的发病机制有着密切的关系,为治疗瘢痕疙瘩提供了一个潜在的候选靶点。
基金funding from the Basic Research Project of the Education Department of Shaanxi Province(21JC010,21JP035)the Young and Middle-Aged Scientific Research and Innovation Team of the Shaanxi Provincial Administration of Traditional Chinese Medicine(2022SLRHLJ001)the 2023 Central Financial Transfer Payment Local Project“Innovation and Improvement of Five Types of Hospital Preparations,Such as Roumudan Granules”.
文摘Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.
文摘[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用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)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。
文摘目的:研究隔药灸治疗子宫内膜异位症大鼠模型的疗效及机制。方法:构建子宫内膜异位症大鼠模型并随机分为治疗组、孕三烯酮组、模型组和假手术组。经治疗后,采集大鼠病灶标本,观察隔药灸对大鼠异位子宫内膜体积的抑制作用,计算抑制率;RT-PCR法检测各组大鼠异位子宫内膜的KDR和PTGS2 m RNA表达。结果:经隔药灸治疗后大鼠模型的异位子宫内膜体积较模型组明显缩小;治疗组大鼠模型的异位子宫内膜PTGS2和KDRm RNA表达均明显低于模型组。结论:隔药灸能明显抑制大鼠模型异位子宫内膜的发展,并且这种治疗作用可能与抑制KDR和PTGS2表达,从而调控异位子宫内膜血管生成有关。