Objective： To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule （清络通痹颗粒, QTG） on osteoclast differentiation in rheumatoid arthritis in rats. Methods： Fibroblast and monocyte co-c...Objective： To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule （清络通痹颗粒, QTG） on osteoclast differentiation in rheumatoid arthritis in rats. Methods： Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic （AIA） rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptorassociated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 （TRAF6/ MAPK/NFATcl） pathways was examined. Results： The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase （TRAP） staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase （ERK）1/2, c-Jun N-terminal kinase （JNK） and p38 and decreased the percentage of cells with nuclear NFATcl in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity （P〈0.01 and P〈0.05, respectively）. After the addition of MAPK inhibitors, the NFATcl expression showed no significant difference compared with the control group （P〉0.05）. Conclusions： Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATcl pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.展开更多
该文首次提出基于网络靶标理论与技术的名医临床验方优化开发新方法,并以“清络饮”优化与开发为范例,建立一种科学手段与人用经验有机结合的中医药精准研发新途径。该研究以清络饮组方为基础,利用该课题组自主研发的网络靶标分析专利技...该文首次提出基于网络靶标理论与技术的名医临床验方优化开发新方法,并以“清络饮”优化与开发为范例,建立一种科学手段与人用经验有机结合的中医药精准研发新途径。该研究以清络饮组方为基础,利用该课题组自主研发的网络靶标分析专利技术UNIQ(using network target for intelligent and quantitative analysis on drug actions)系统,从现有中药中全面预测出能够靶向类风湿性关节炎(rheumatoid arthritis,RA)血管新生等关键信号通路的备选中药,结合首届国医大师李济仁、安徽省名中医李艳学术经验从中医理论角度遣方组药,优化开发出一种靶向RA血管新生的新处方“加味清络饮”,进而验证加味清络饮的临床疗效与作用机制。结果显示,通过UNIQ系统预测出27味对RA血管新生等关键信号通路具有调节作用的备选中药,其中6味中药被名医按照中医理论选择而获得加味清络饮新组方;临床试验结果显示,加味清络饮在美国风湿病学会RA疾病缓解标准(American college of rheumatology 20、50 criteria,ACR20、ACR50)、中医证候疗效评价等方面的临床疗效均优于清络饮;机制研究结果显示,加味清络饮可靶向血管内皮生长因子VEGF信号转导通路、NF-κB通路、炎症细胞因子释放、免疫调节等不同通路,发挥抑制RA炎症反应、血管新生的网络调节机制。该研究靶向RA特定生物网络对名方进行精准优化,研制出了临床疗效提升、临床定位较为清晰、并获专利授权的加味清络饮新方,为名医经验传承发展和中药精准研发提供了新的思路和途径。展开更多
基金Supported by the National Natural Science Foundation of China(No.81072749)the Ministry of Education of Overseas Returnees Research Fund(No.2006331)+3 种基金Six Talent Peaks Subject of Jiangsu Province(No.2007)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.20116)Jiangsu Province Ordinary University Innovative Research ProjectOrdinary University Innovative Research Project of Jiangsu Province(No.2011)
文摘Objective： To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule （清络通痹颗粒, QTG） on osteoclast differentiation in rheumatoid arthritis in rats. Methods： Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic （AIA） rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptorassociated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 （TRAF6/ MAPK/NFATcl） pathways was examined. Results： The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase （TRAP） staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase （ERK）1/2, c-Jun N-terminal kinase （JNK） and p38 and decreased the percentage of cells with nuclear NFATcl in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity （P〈0.01 and P〈0.05, respectively）. After the addition of MAPK inhibitors, the NFATcl expression showed no significant difference compared with the control group （P〉0.05）. Conclusions： Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATcl pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.
文摘该文首次提出基于网络靶标理论与技术的名医临床验方优化开发新方法,并以“清络饮”优化与开发为范例,建立一种科学手段与人用经验有机结合的中医药精准研发新途径。该研究以清络饮组方为基础,利用该课题组自主研发的网络靶标分析专利技术UNIQ(using network target for intelligent and quantitative analysis on drug actions)系统,从现有中药中全面预测出能够靶向类风湿性关节炎(rheumatoid arthritis,RA)血管新生等关键信号通路的备选中药,结合首届国医大师李济仁、安徽省名中医李艳学术经验从中医理论角度遣方组药,优化开发出一种靶向RA血管新生的新处方“加味清络饮”,进而验证加味清络饮的临床疗效与作用机制。结果显示,通过UNIQ系统预测出27味对RA血管新生等关键信号通路具有调节作用的备选中药,其中6味中药被名医按照中医理论选择而获得加味清络饮新组方;临床试验结果显示,加味清络饮在美国风湿病学会RA疾病缓解标准(American college of rheumatology 20、50 criteria,ACR20、ACR50)、中医证候疗效评价等方面的临床疗效均优于清络饮;机制研究结果显示,加味清络饮可靶向血管内皮生长因子VEGF信号转导通路、NF-κB通路、炎症细胞因子释放、免疫调节等不同通路,发挥抑制RA炎症反应、血管新生的网络调节机制。该研究靶向RA特定生物网络对名方进行精准优化,研制出了临床疗效提升、临床定位较为清晰、并获专利授权的加味清络饮新方,为名医经验传承发展和中药精准研发提供了新的思路和途径。
