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基于网络药理学及外周血基因芯片技术探究温阳益气活血方治疗慢性心衰的作用机制 被引量:17
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作者 吕李飞 吴俊松 +5 位作者 苟江腾 赵成周 孙胜男 李忠宽 贾守宁 祁永福 《中草药》 CAS CSCD 北大核心 2021年第18期5626-5642,共17页
目的基于网络药理学与分子对接技术,预测名中医验方温阳益气活血方治疗慢性心衰的物质基础及作用机制,通过实验探讨温阳益气活血方对慢性心衰患者外周血基因表达谱的影响,为中医药治疗慢性心衰的后续研究提供基础与方向。方法通过中药... 目的基于网络药理学与分子对接技术,预测名中医验方温阳益气活血方治疗慢性心衰的物质基础及作用机制,通过实验探讨温阳益气活血方对慢性心衰患者外周血基因表达谱的影响,为中医药治疗慢性心衰的后续研究提供基础与方向。方法通过中药系统药理学分析平台(TCMSP)筛选温阳益气活血方中潜在活性成分;GEO数据库获得潜在活性成分的作用靶点;Venny在线平台获得慢性心衰的主要致病靶标。利用STRING数据库和Cytoscape软件构建“方药-成分-靶点-疾病”网络模型及蛋白相互作用(protein-protein interaction,PPI)网络图,分析方药中主要活性成分及作用靶点蛋白;使用R语言的Cluster Profiler工具包对方药作用核心靶点进行基因本体论(genetic ontology,GO)及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析。借助Autodock进行分子对接。随机选取30例健康志愿者作为对照组。60例慢性心衰患者入选试验组,按随机分为化学药组和中西药组,各组30例。化学药组采用盐酸贝那普利片(10 mg/d)、氢氯噻嗪片(50 mg/d)、螺内酯片(40 mg/d)、琥珀酸美托洛尔片(23.75 mg/d)及地高辛片(0.125 mg/d)联合用药,1次/d;中西药组在常规化学药物口服治疗的基础上联合温阳益气活血方颗粒剂,6 g/次,2次/d,2组疗程均为15 d。对照组于清晨空腹安静状态下,抗凝管采集前臂静脉血,后随机抽取10例外周血用于基因芯片的差异检测;试验组于入院次日清晨空腹状态下采集,最后随机抽取2组中各5例药物干预前后的外周血用于基因芯片的差异检测。采用Affymetrix公司的PrimeViewTM Human Gene Expression Array基因芯片检测,结合生物信息学的转录组学及RNA技术分析温阳益气活血方的差异表达基因。结果筛选出方药潜在活性成分6个和236个药物靶点;得到方药治疗慢性心衰的潜在作用靶点17个;通过GO分析得出519个生物过程、5个细胞组分、14个分子功能;KEGG通路富集分析得出89条信号通路。2组慢性心衰患者给予不同药物干预后,中西药组外周血基因表达谱中共检测出42640个基因,化学药组为37081个基因,2种干预方法均能影响慢性心衰外周血的基因表达,单纯化学药较中西药联合干预改变慢性心衰的差异基因数目少。相关检测指标血清脑钠肽前体(brain natriuretic peptide,BNP)、中医症状积分及心功能疗效也具有统计学差异(P<0.05)。结论初步揭示了温阳益气活血方干预慢性心衰可能是通过多成分、多靶点、多途径发挥防治作用,其作用机制与ZNF331、TRAPPC10、SMAD7、MYC、RORA、PCNA基因相关,涉及Th17细胞分化、B细胞受体信号通路、腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)通路。 展开更多
关键词 慢性心衰 温阳益气活血方 分子对接 信号通路 网络药理学 基因表达谱芯片
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基于多组学技术探究慢性心衰靶向EGR1中药化合物抑制剂的虚拟筛选 被引量:1
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作者 吕李飞 吴俊松 +5 位作者 苟江腾 赵成周 徐卫松 李忠宽 贾守宁 祁永福 《现代中药研究与实践》 CAS 2022年第2期87-93,共7页
目的探究慢性心衰靶向EGR1中药化合物抑制剂的筛选。方法选取基因芯片中慢性心衰患者与健康人差异表达上调最显著的EGR1基因,再以6种治疗药物作为阳性对照,分析其与EGR1的作用模式,并推测拟筛的化合物与阳性对照物是否具有相似的活性。... 目的探究慢性心衰靶向EGR1中药化合物抑制剂的筛选。方法选取基因芯片中慢性心衰患者与健康人差异表达上调最显著的EGR1基因,再以6种治疗药物作为阳性对照,分析其与EGR1的作用模式,并推测拟筛的化合物与阳性对照物是否具有相似的活性。最后取空白组、模型组及巴西苏木素组大鼠血浆,采用质谱技术联合代谢组学Meta X软件对质谱数据进行多元统计分析,寻找出差异代谢物,再基于KEGG数据库进行代谢物通路注释。结果通过SP、XP打分,将最初30000个小分子化合物筛为100个,再通过结合模式评估筛选出巴西苏木素。三组大鼠血浆代谢组学共鉴定出209个差异代谢物,涉及氨基酸类、脂质类、萜类类和黄酮类。整合多组学研究结果,初步证实巴西苏木素可干预慢性心衰。结论靶向EGR1抑制剂的巴西苏木素可基于糖脂及氨基酸代谢紊乱干预慢性心衰,这与苯丙氨酸代谢、酪氨酸合成、2-氧代羧酸代谢相关。 展开更多
关键词 慢性心衰 基因芯片 多组学 虚拟筛选 EGR1 巴西苏木素
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Risk factors of mortality in road traffic injury patients with acute respiratory distress syndrome 被引量:11
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作者 ZHAO Xiao-gang wu jun-song +5 位作者 HE Xiao-di MA Yue-feng ZHANG Mao GAN Jian-xin XU Shao-wen JIANG Guan-yu 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第11期968-972,共5页
Background Among the deaths due to trauma, about one half of the patients suffer from road traffic injury (RTI). Most of RTI patients complicate acute respiratory distress syndrome (ARDS) and severe multiple injur... Background Among the deaths due to trauma, about one half of the patients suffer from road traffic injury (RTI). Most of RTI patients complicate acute respiratory distress syndrome (ARDS) and severe multiple injuries. ARDS is a major contributor to morbidity and mortality in trauma patients. Although many injuries and conditions are believed to be associated with ARDS independent risk factors in trauma patients, their relative importance in development of the syndrome are undefined. We hypothesize that not all of the traditional risk factors impacting mortality are independently associated with patients strictly identified by traffic injury. This study aimed to sieve distinctive risk factors in our RTI population, meanwhile, we also hypothesize that there may exist significantly different risk factors in these patients.Methods This was a retrospective cohort study regarding RTI as a single cause for emergency intensive care unit (EICU) admission. Patients identified as severe RTI with post-traumatic ARDS were enrolled in a prospectively maintained database between May 2002 and April 2007 and observed. Twenty-three items of potential risk impacting mortality were calculated by univariate and multivariate Logistic analyses in order to find distinctive items in these severe RTI patients. Results There were 247 RTI patients with post-traumatic ARDS admitted to EICU during the study period. The unadjusted odds ratio (OR) and 95% confidence intervals (CI) of mortality were associated with six risk factors out of 23: APACHE II score, duration of trauma factor, pulmonary contusion, aspiration of gastric contents, sepsis and duration of mechanical ventilation. The adjusted ORs with 95% Cl were denoted with respect to surviving beyond 96 hours EICU admission (APACHE II score, duration of trauma factor, aspiration of gastric contents), APACHE II score beyond 20 EICU admission (duration of trauma factor, sepsis, duration of mechanical ventilation) and mechanical ventilation beyond 7 days EICU admission (duration of trauma factor and sepsis). Conclusions We have retrospectively demonstrated an adverse effect of six different risk factors out of 23 items in mortality of post-traumatic ARDS within severe RTI patients and, moreover, gained distinct outcomes in stratified patients under real emergency trauma circumstance. An impact of APACHE II score and pulmonary contusion contributing to prediction of mortality may exist in prophase after traffic injury. Sepsis is still a vital risk factor referring to systemic inflammatory response syndrome, infection, and secondary multiple organs dysfunction. Eliminating trauma factors as early as possible becomes the critical therapeutic measure. Aspiration of gastric contents could lead to incremental mortality due to severe ventilation associated pneumonia. Long-standing mechanical ventilation should be constrained on account of severe refractory complications. 展开更多
关键词 acute respiratory distress syndrome road traffic injury risk factors MORTALITY
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