通过网络药理学来预测复方鹿茸健骨胶囊(CLJC)治疗老年性骨质疏松(Senile Osteoporosis,SOP)的作用机制。通过中药系统药理学成分分析平台(BATMAN-TCM)、TCMID数据库、中国知网、PubMed和Web of Science等途径查阅相关文献,中药系统药...通过网络药理学来预测复方鹿茸健骨胶囊(CLJC)治疗老年性骨质疏松(Senile Osteoporosis,SOP)的作用机制。通过中药系统药理学成分分析平台(BATMAN-TCM)、TCMID数据库、中国知网、PubMed和Web of Science等途径查阅相关文献,中药系统药理学数据库(TCMSP)检索CLJC的主要活性成分,ADME功能以及Uniprot数据库检索筛选CLJC的主要活性成分靶点;通过GeneCards、在线人类孟德尔遗传数据库(OMIM)、疾病相关的基因与突变位点数据库(DisGeNET)检索SOP主要作用靶点;通过Venny2.1.0软件对药物靶点与疾病靶点取交集,两者交集即为CLJC治疗SOP潜在靶点;用STRING数据库分析蛋白质-蛋白质相互作用(PPI),并且构建PPI网络图;用Metascape数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,并通过Cytoscape 3.9.2软件构建“药物成分-靶点-疾病-通路”网络图;最后,通过Auto Dock Tools 1.5.7软件将核心活性成分与核心靶点进行分子对接,并进一步验证CLJC治疗SOP以及网络药理学所得出的结论。CLJC共筛选到89种活性成分,相对应的药物靶点有463个;SOP共筛选到972个疾病靶点;CLJC与SOP共有81个靶点,核心靶点有AKT1、TP53、CTNNB1、SRC、RXRA、ITGB3、SP1、MMP3、TNF、MMP9、MMP2、TGFB1、PPARG、FOS、IGF2、VEGFA和IL10等;GO分析显示,BP有激素反应(Response to hormone)、肽反应(Response to peptide)、细胞对氮化合物的反应(Cellular response to nitrogen compound)等;MF有信号受体调节器活性(Signaling receptor regulator activity)、信号受体激活器活性(Signaling receptor activator activity)、受体配体活性(Receptor ligand activity)等;CC有隔膜筏(Membrane raft)、膜微结构域(Membrane microdomain)、质膜筏(Plasma membrane raft)等;KEGG富集分析共得到164条通路,主要有癌症通路(Pathways in cancer)、MAPK信号通路(MAPK signaling pathway)、癌症蛋白聚糖(Proteoglycans in cancer)以及脂质和动脉粥样硬化(Lipid and atherosclerosis)等;分子对接验证核心活性成分与核心靶点都表现出良好的对接活性。本研究证实了CLJC中的quercetin成分与AKT1和TP53靶蛋白相互作用,通过Pathways in cancer、MAPK signaling pathway等信号通路多成分、多靶点、多通路治疗SOP。展开更多
Floodplains are important and distinctive ecosystems around the world,and the recruitment of ichthyoplankton from river to floodplain lakes is crucial to maintain this unique ecosystem.However,this process has not bee...Floodplains are important and distinctive ecosystems around the world,and the recruitment of ichthyoplankton from river to floodplain lakes is crucial to maintain this unique ecosystem.However,this process has not been well documented.In this study,ichthyoplankton were sampled to investigate the details of ichthyoplankton recruitment from the Changjiang(Yangtze)River to the Dongting Lake via a floodway channel,the Songzi River,from May to July in 2013 and 2014.During the study period,41 species of eggs and larvae were sampled.Among the samples,16 were river-lake migratory species(RL),representing 23.5%of the species in the Dongting Lake.In 2013,an estimated 130 million eggs and 3180 million larvae drifted through the sampling section,and in 2014,an estimated 1 060 million eggs and 1040 million larvae drifted through the sampling section.The amount of eggs and larvae of RL reached 3 210 million in 2013 and 1 850 million in 2014,respectively.These results demonstrated the importance of ichthyoplankton recruitment from the river to the lake,as species diversity will decrease sharply without this recruitment.Canonical correspondence analysis(CCA)showed that water temperature and water flow are the two most important factors influencing the spawning activities of fish.To maintain the high fish diversity in the Changjiang floodplain,we suggest to irrigate the channel to increase water discharge and increase the transport of ichthyoplankton from the Changjiang mainstream into the Dongting Lake.展开更多
目的:通过观察大黄泄浊方对5/6肾切除大鼠肾脏病理变化,肾组织活性氧(ROS)/硫氧还蛋白互作蛋白(TXNIP)/NOD样受体蛋白3(NLRP3)通路表达的变化,研究其保护肾功能,延缓肾间质纤维化的作用机制及可能性。方法:90只健康SD雄性大鼠随机分为...目的:通过观察大黄泄浊方对5/6肾切除大鼠肾脏病理变化,肾组织活性氧(ROS)/硫氧还蛋白互作蛋白(TXNIP)/NOD样受体蛋白3(NLRP3)通路表达的变化,研究其保护肾功能,延缓肾间质纤维化的作用机制及可能性。方法:90只健康SD雄性大鼠随机分为假手术组、模型组、大黄泄浊方低、中、高剂量(6.825、13.65、27.30 g·kg^(-1))组和尿毒清颗粒(2.60 g·kg^(-1))组。除假手术组外其余5组均采用5/6肾切除术复制CRF大鼠模型。造模成功后,各给药组分别给予相应剂量的药物混悬液灌胃,每日1次,连续8周。给药结束后,检测大鼠血清中肌酐(SCr)、尿素氮(BUN)水平和24 h尿蛋白定量(UTP)水平;蛋白免疫印迹法(Western blot)检测硫氧还蛋白(TRX)、TXNIP和NLRP3蛋白的表达情况;免疫组化法检测NLRP3、TRX、TXNIP、接头蛋白凋亡相关斑点样蛋白(ASC)、转化生长因子-β(TGF-β)、Ⅳ型胶原蛋白(CollagenⅣ)、α-平滑肌肌动蛋白(α-SMA)和调纤连蛋白(FN)的表达。结果:与假手术组比较,模型组大鼠血SCr、BUN、24 h UTP水平明显增高(P<0.05),TRX、TXNIP、NLRP3、ASC、TGF-β、CollagenⅣ、α-SMA和FN蛋白显著增高(P<0.01),肾间质发生显著纤维化;与模型组比较,大黄泄浊方各剂量组和尿毒清颗粒组血SCr、BUN、24 h UTP水平均有不同程度降低(P<0.05),TRX、TXNIP、NLRP3、ASC、TGF-β、CollagenⅣ、α-SMA和FN蛋白显著降低(P<0.01),肾间质纤维化不同程度改善。结论:大黄泄浊方可保护慢性肾衰竭大鼠肾功能、延缓肾间质纤维化。展开更多
文摘通过网络药理学来预测复方鹿茸健骨胶囊(CLJC)治疗老年性骨质疏松(Senile Osteoporosis,SOP)的作用机制。通过中药系统药理学成分分析平台(BATMAN-TCM)、TCMID数据库、中国知网、PubMed和Web of Science等途径查阅相关文献,中药系统药理学数据库(TCMSP)检索CLJC的主要活性成分,ADME功能以及Uniprot数据库检索筛选CLJC的主要活性成分靶点;通过GeneCards、在线人类孟德尔遗传数据库(OMIM)、疾病相关的基因与突变位点数据库(DisGeNET)检索SOP主要作用靶点;通过Venny2.1.0软件对药物靶点与疾病靶点取交集,两者交集即为CLJC治疗SOP潜在靶点;用STRING数据库分析蛋白质-蛋白质相互作用(PPI),并且构建PPI网络图;用Metascape数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,并通过Cytoscape 3.9.2软件构建“药物成分-靶点-疾病-通路”网络图;最后,通过Auto Dock Tools 1.5.7软件将核心活性成分与核心靶点进行分子对接,并进一步验证CLJC治疗SOP以及网络药理学所得出的结论。CLJC共筛选到89种活性成分,相对应的药物靶点有463个;SOP共筛选到972个疾病靶点;CLJC与SOP共有81个靶点,核心靶点有AKT1、TP53、CTNNB1、SRC、RXRA、ITGB3、SP1、MMP3、TNF、MMP9、MMP2、TGFB1、PPARG、FOS、IGF2、VEGFA和IL10等;GO分析显示,BP有激素反应(Response to hormone)、肽反应(Response to peptide)、细胞对氮化合物的反应(Cellular response to nitrogen compound)等;MF有信号受体调节器活性(Signaling receptor regulator activity)、信号受体激活器活性(Signaling receptor activator activity)、受体配体活性(Receptor ligand activity)等;CC有隔膜筏(Membrane raft)、膜微结构域(Membrane microdomain)、质膜筏(Plasma membrane raft)等;KEGG富集分析共得到164条通路,主要有癌症通路(Pathways in cancer)、MAPK信号通路(MAPK signaling pathway)、癌症蛋白聚糖(Proteoglycans in cancer)以及脂质和动脉粥样硬化(Lipid and atherosclerosis)等;分子对接验证核心活性成分与核心靶点都表现出良好的对接活性。本研究证实了CLJC中的quercetin成分与AKT1和TP53靶蛋白相互作用,通过Pathways in cancer、MAPK signaling pathway等信号通路多成分、多靶点、多通路治疗SOP。
基金Supported by the National Key Research and Development Program of China(No.2016YFC0402005)the Three Gorges Project EcoEnvironmental Monitoring System(No.JJ [2017]-011)+1 种基金the National Natural Science Foundation of China(No.NSFC31400359)the China Three Gorges Corporation(No.0704097)
文摘Floodplains are important and distinctive ecosystems around the world,and the recruitment of ichthyoplankton from river to floodplain lakes is crucial to maintain this unique ecosystem.However,this process has not been well documented.In this study,ichthyoplankton were sampled to investigate the details of ichthyoplankton recruitment from the Changjiang(Yangtze)River to the Dongting Lake via a floodway channel,the Songzi River,from May to July in 2013 and 2014.During the study period,41 species of eggs and larvae were sampled.Among the samples,16 were river-lake migratory species(RL),representing 23.5%of the species in the Dongting Lake.In 2013,an estimated 130 million eggs and 3180 million larvae drifted through the sampling section,and in 2014,an estimated 1 060 million eggs and 1040 million larvae drifted through the sampling section.The amount of eggs and larvae of RL reached 3 210 million in 2013 and 1 850 million in 2014,respectively.These results demonstrated the importance of ichthyoplankton recruitment from the river to the lake,as species diversity will decrease sharply without this recruitment.Canonical correspondence analysis(CCA)showed that water temperature and water flow are the two most important factors influencing the spawning activities of fish.To maintain the high fish diversity in the Changjiang floodplain,we suggest to irrigate the channel to increase water discharge and increase the transport of ichthyoplankton from the Changjiang mainstream into the Dongting Lake.
文摘目的:通过观察大黄泄浊方对5/6肾切除大鼠肾脏病理变化,肾组织活性氧(ROS)/硫氧还蛋白互作蛋白(TXNIP)/NOD样受体蛋白3(NLRP3)通路表达的变化,研究其保护肾功能,延缓肾间质纤维化的作用机制及可能性。方法:90只健康SD雄性大鼠随机分为假手术组、模型组、大黄泄浊方低、中、高剂量(6.825、13.65、27.30 g·kg^(-1))组和尿毒清颗粒(2.60 g·kg^(-1))组。除假手术组外其余5组均采用5/6肾切除术复制CRF大鼠模型。造模成功后,各给药组分别给予相应剂量的药物混悬液灌胃,每日1次,连续8周。给药结束后,检测大鼠血清中肌酐(SCr)、尿素氮(BUN)水平和24 h尿蛋白定量(UTP)水平;蛋白免疫印迹法(Western blot)检测硫氧还蛋白(TRX)、TXNIP和NLRP3蛋白的表达情况;免疫组化法检测NLRP3、TRX、TXNIP、接头蛋白凋亡相关斑点样蛋白(ASC)、转化生长因子-β(TGF-β)、Ⅳ型胶原蛋白(CollagenⅣ)、α-平滑肌肌动蛋白(α-SMA)和调纤连蛋白(FN)的表达。结果:与假手术组比较,模型组大鼠血SCr、BUN、24 h UTP水平明显增高(P<0.05),TRX、TXNIP、NLRP3、ASC、TGF-β、CollagenⅣ、α-SMA和FN蛋白显著增高(P<0.01),肾间质发生显著纤维化;与模型组比较,大黄泄浊方各剂量组和尿毒清颗粒组血SCr、BUN、24 h UTP水平均有不同程度降低(P<0.05),TRX、TXNIP、NLRP3、ASC、TGF-β、CollagenⅣ、α-SMA和FN蛋白显著降低(P<0.01),肾间质纤维化不同程度改善。结论:大黄泄浊方可保护慢性肾衰竭大鼠肾功能、延缓肾间质纤维化。
