目的:基于网络药理学与细胞实验探讨加味黄芪桂枝五物汤治疗类风湿关节炎(rheumatoid arthritis, RA)的作用机制。方法: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 ...目的:基于网络药理学与细胞实验探讨加味黄芪桂枝五物汤治疗类风湿关节炎(rheumatoid arthritis, RA)的作用机制。方法: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)、BATMAN-TCM数据库检索并筛选加味黄芪桂枝五物汤的活性成分和作用靶点。在GeneCards数据库、OMIM数据库检索RA的作用靶点,将加味黄芪桂枝五物汤与RA的靶点取交集。通过Bioconductor平台和R软件对交集基因进行基因本体(Gene Ontology, GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)分析。将20只SD大鼠随机分为加味黄芪桂枝五物汤组(1.8 g·kg^(-1))和正常组,每组各10只。灌胃7 d后,制备体积分数为5%、10%、20%的含药血清。利用CCK-8法检测MH7A细胞的增殖情况;Annexin V-PI双染色法检测MH7A细胞凋亡情况;Western Blot检测MH7A细胞磷脂酰肌醇-3-激酶(phosphatidylinositol-3-hydroxykinase, PI3K)、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-AKT)蛋白表达水平;ELISA检测MH7A细胞白细胞介素-17(interleukin-17,IL-17)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量。结果:共检索加味黄芪桂枝五物汤的活性成分141个,作用靶点303个。RA的作用靶点4 937个,加味黄芪桂枝五物汤与RA的交集靶点127个。GO分析主要涉及对脂多糖的反应、对细胞增殖的负反馈调节、对细胞因子的反应、细胞活化调节、细胞凋亡过程的正调节等。KEGG通路主要包括PI3K/AKT信号通路、TNF信号通路、钙信号通路等。细胞培养12 h、24 h、48 h时,与对照组比较,加味黄芪桂枝五物汤高剂量组、中剂量组与低剂量组细胞的增殖抑制率升高(P<0.05)。细胞培养24 h时,与对照组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞凋亡率增加(P<0.05)。与对照组比较,模型组细胞PI3K、p-AKT表达水平升高(P<0.05);与模型组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞PI3K、p-AKT表达水平降低(P<0.05)。与对照组比较,模型组细胞IL-17、TNF-α、IL-6含量升高(P<0.05);与模型组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞IL-17、TNF-α、IL-6含量下降(P<0.05)。结论:加味黄芪桂枝五物汤可能通过调节PI3K/AKT信号通路等相关途径、抑制MH7A细胞增殖、促进细胞凋亡、降低炎症因子水平,从而发挥抗RA的作用。展开更多
Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with inject...Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with injection of streptozotocin and fed on high calorie diet to study the effects of STHCQDon the release of insulin sensitivity. Results: (l ) Fasting serum glucose, serum insulin, intake of food and waterwere significantly decreased (P < 0. 05 -- 0. 01 ) in STHCQD-treated diabetic rats as compared with untreated diabetic rats, while the insulin sensitivity was significantly increased (P < 0. 05 ). (2) The liver cell membranesfrom STHCQD-treated diabetic rats released the quantity of insulin receptor which inhibited adenylate cyclaseactivity, but this effect was blunted in untreated diabetic rats (P < 0. 05). (3) A significantly increased glucoseoxidation in adipocyte of STHCQD-treated diabetic rats was found as compared with those of untreated diabeticrats (P< 0. 05). Conclusions: STHCQD therapy Increased sensitivity and responsiveness of target cells to insulin, i. e. it might decrease insulin resistance at receptor sites and POst--receptor sites in rats with NIDDM, butcould not.reverse the insulin resistance.展开更多
文摘目的:基于网络药理学与细胞实验探讨加味黄芪桂枝五物汤治疗类风湿关节炎(rheumatoid arthritis, RA)的作用机制。方法: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)、BATMAN-TCM数据库检索并筛选加味黄芪桂枝五物汤的活性成分和作用靶点。在GeneCards数据库、OMIM数据库检索RA的作用靶点,将加味黄芪桂枝五物汤与RA的靶点取交集。通过Bioconductor平台和R软件对交集基因进行基因本体(Gene Ontology, GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)分析。将20只SD大鼠随机分为加味黄芪桂枝五物汤组(1.8 g·kg^(-1))和正常组,每组各10只。灌胃7 d后,制备体积分数为5%、10%、20%的含药血清。利用CCK-8法检测MH7A细胞的增殖情况;Annexin V-PI双染色法检测MH7A细胞凋亡情况;Western Blot检测MH7A细胞磷脂酰肌醇-3-激酶(phosphatidylinositol-3-hydroxykinase, PI3K)、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-AKT)蛋白表达水平;ELISA检测MH7A细胞白细胞介素-17(interleukin-17,IL-17)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量。结果:共检索加味黄芪桂枝五物汤的活性成分141个,作用靶点303个。RA的作用靶点4 937个,加味黄芪桂枝五物汤与RA的交集靶点127个。GO分析主要涉及对脂多糖的反应、对细胞增殖的负反馈调节、对细胞因子的反应、细胞活化调节、细胞凋亡过程的正调节等。KEGG通路主要包括PI3K/AKT信号通路、TNF信号通路、钙信号通路等。细胞培养12 h、24 h、48 h时,与对照组比较,加味黄芪桂枝五物汤高剂量组、中剂量组与低剂量组细胞的增殖抑制率升高(P<0.05)。细胞培养24 h时,与对照组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞凋亡率增加(P<0.05)。与对照组比较,模型组细胞PI3K、p-AKT表达水平升高(P<0.05);与模型组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞PI3K、p-AKT表达水平降低(P<0.05)。与对照组比较,模型组细胞IL-17、TNF-α、IL-6含量升高(P<0.05);与模型组比较,加味黄芪桂枝五物汤低剂量组、中剂量组、高剂量组细胞IL-17、TNF-α、IL-6含量下降(P<0.05)。结论:加味黄芪桂枝五物汤可能通过调节PI3K/AKT信号通路等相关途径、抑制MH7A细胞增殖、促进细胞凋亡、降低炎症因子水平,从而发挥抗RA的作用。
文摘Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with injection of streptozotocin and fed on high calorie diet to study the effects of STHCQDon the release of insulin sensitivity. Results: (l ) Fasting serum glucose, serum insulin, intake of food and waterwere significantly decreased (P < 0. 05 -- 0. 01 ) in STHCQD-treated diabetic rats as compared with untreated diabetic rats, while the insulin sensitivity was significantly increased (P < 0. 05 ). (2) The liver cell membranesfrom STHCQD-treated diabetic rats released the quantity of insulin receptor which inhibited adenylate cyclaseactivity, but this effect was blunted in untreated diabetic rats (P < 0. 05). (3) A significantly increased glucoseoxidation in adipocyte of STHCQD-treated diabetic rats was found as compared with those of untreated diabeticrats (P< 0. 05). Conclusions: STHCQD therapy Increased sensitivity and responsiveness of target cells to insulin, i. e. it might decrease insulin resistance at receptor sites and POst--receptor sites in rats with NIDDM, butcould not.reverse the insulin resistance.