目的通过网络药理学方法探讨川芎嗪治疗冠心病的分子机制。方法利用Pharmmapper数据库、中药分子机制生物学分析平台(BATMAN-TCM)预测化合物靶点,通过与人类基因数据库(Genecards)、在线人类孟德尔遗传数据库(OMIM)治疗冠心病的相关靶...目的通过网络药理学方法探讨川芎嗪治疗冠心病的分子机制。方法利用Pharmmapper数据库、中药分子机制生物学分析平台(BATMAN-TCM)预测化合物靶点,通过与人类基因数据库(Genecards)、在线人类孟德尔遗传数据库(OMIM)治疗冠心病的相关靶点进行匹配,得到化合物-疾病共同靶蛋白。利用Cytoscape3.7.1软件构建化合物-靶点网络,然后借助STRING数据库进行蛋白互作网络分析,最后利用R语言进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果经过筛选得到川芎嗪作用于冠心病的靶点115个,这些靶点主要富集在磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI3K-Akt)、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等多条信号通路上。结论川芎嗪可能主要通过抗凋亡、抗凝血、抗炎、促进血管新生、应对缺氧等多方面对冠心病进行干预,体现了中药多靶点、多通路的作用特点。展开更多
目的观察柴胡加龙骨牡蛎汤(CHLM)对心肌梗死合并焦虑大鼠肠道屏障、内毒素(lipopolysaccharides,LPS)/核因子κB(nuclear transcription factor-κB,NF-κB)介导的心肌炎性损伤、心脏收缩功能、行为学、血清炎症因子的影响。方法将24只...目的观察柴胡加龙骨牡蛎汤(CHLM)对心肌梗死合并焦虑大鼠肠道屏障、内毒素(lipopolysaccharides,LPS)/核因子κB(nuclear transcription factor-κB,NF-κB)介导的心肌炎性损伤、心脏收缩功能、行为学、血清炎症因子的影响。方法将24只雄性SD大鼠随机分为假手术组、模型组、中药组。其中模型组,中药组接受为期3周的焦虑造模,在第2周末模型组及中药组进行心梗造模。假手术组正常饮水,仅挂线,不结扎。术后第二天,中药组予柴胡加龙骨牡蛎汤13.6 g/kg灌胃。模型组及假手术组予等体积生理盐水灌胃。检测大鼠垂直运动分数、水平运动分数、开放臂进入次数百分比(the percentage of open arm entry,OE%)、开放臂进入时间百分比(the percentage of open arm time,OT%)等行为学指标,检测大鼠左室射血分数(left ventricular injection fraction,LVEF)、左室缩短分数(left ventricular systolic function,LVFS)、左心室舒张末期内径(left ventricular internal diameter at end-diastole,LVIDd)和左心室收缩末期内径(left ventricular internal diameter at end-systole,LVIDs)等超声指标。对心脏组织石蜡切片进行苏木精—伊红(hematoxylin-eosin,HE)染色后观察。用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)测定血清LPS及炎性因子水平,用蛋白免疫印迹法(Western-blot,WB)检测心肌组织NF-κB信号通路相关蛋白表达。结果(1)取样前,假手术组7只大鼠存活,模型组,中药组各6只大鼠存活。(2)肠道屏障指标:与模型组相比,中药组闭合蛋白(occludin)、闭锁连接蛋白-1(zonula occludens-1,ZO-1)表达升高,差异具有显著统计学意义。中药组紧密连接蛋白-1(claudin-1)表达相对模型组有升高趋势,但差异无统计学意义。(3)NF-κB相关蛋白:与模型组相比,中药组NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、磷酸化的核因子κB p65与核因子κB p65的比值(ratio of NF-κB pp65 to NF-κB p65,NF-κB pp65/p65)、白细胞介素1β(interleukin-1β,IL-1β)表达下调具有显著统计学意义。核因子κB抑制蛋白α(inhibitory subunit of NF-κB alpha,IκBα)表达上调具有统计学意义。(4)行为学指标:与模型组相比,中药组OE%、OT%、垂直运动评分、水平运动评分升高且具有统计学意义;(5)心功能指标:与模型组相比,中药组LVEF、LVFS升高且均具有统计学意义,LVIDs降低且具有统计学意义,LVIDd有下降趋势,但无统计学差异。(6)血清学指标:与模型组相比,中药组LPS、IL-1β、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)下降具有统计学意义,白细胞介素6(interleukin-6,IL-6)下降具有显著统计学意义。结论柴胡加龙骨牡蛎汤能够改善心肌梗死合并焦虑模型大鼠的肠道屏障损伤、心肌炎性损伤,增强左室收缩功能,减轻焦虑行为,其机制可能与肠道屏障及LPS/NF-κB信号介导的炎症反应相关。展开更多
OBJECTIVE:To evaluated the effectiveness and safety of Chinese herbal medicines(CHMs)for coronary heart disease(CHD)complicated with anxiety.METHODS:Randomized controlled clinical trials(RCTs)with parallel-groups were...OBJECTIVE:To evaluated the effectiveness and safety of Chinese herbal medicines(CHMs)for coronary heart disease(CHD)complicated with anxiety.METHODS:Randomized controlled clinical trials(RCTs)with parallel-groups were included after searching through electric-databases from inception to May,2017.Meta-analysis was undertaken with Rev Man 5.3 software.RESULTS:Twenty-three RCTs enrolling 1654 patients were included in this systematic review.The combination therapy(CHMs combined with anxiolytic)appeared to be superior to anxiolytic in terms of reducing the score of Zung Self-rating Anxiety scale(SAS)(mean Difference(MD),-12.25;95%confidence interval(CI),-14.01 to-10.48,eliminating method;MD,-3.92;95%CI,-5.48 to-2.35,tranquilizing method),improving the total effect rate(relative risk(RR),1.26;95%CI,1.08 to 1.46,eliminating method)and reducing the TCM symptoms scores(MD,-2.24;95%CI,-4.25 to-0.23,tranquilizing method)with a lower incidence of adverse events(RR,0.46;95%CI,0.25 to 0.85,tonifying method).CHMs demonstrated benefits in lowering the score of Hamilton Anxiety Rating scale(MD,-6.77;95%CI,-8.16 to-5.37,tonifying method),lowering the score of SAS(MD,-10.1;95%CI,-13.73 to-6.30,tonifying method)and reducing the TCM symptoms scores(MD,-2.18;95%CI,-3.12 to-1.24,tranquilizing method).CONCLUSION:We got a low evidence that CHMs,which had less side effects,showed potentially benefits to patients with CHD complicated with anxiety.While the results should be interpreted with caution.Trails with higher quality are required to verify the effectiveness and safety of CHMs for CHD complicated with anxiety.展开更多
文摘目的通过网络药理学方法探讨川芎嗪治疗冠心病的分子机制。方法利用Pharmmapper数据库、中药分子机制生物学分析平台(BATMAN-TCM)预测化合物靶点,通过与人类基因数据库(Genecards)、在线人类孟德尔遗传数据库(OMIM)治疗冠心病的相关靶点进行匹配,得到化合物-疾病共同靶蛋白。利用Cytoscape3.7.1软件构建化合物-靶点网络,然后借助STRING数据库进行蛋白互作网络分析,最后利用R语言进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果经过筛选得到川芎嗪作用于冠心病的靶点115个,这些靶点主要富集在磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI3K-Akt)、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等多条信号通路上。结论川芎嗪可能主要通过抗凋亡、抗凝血、抗炎、促进血管新生、应对缺氧等多方面对冠心病进行干预,体现了中药多靶点、多通路的作用特点。
文摘目的观察柴胡加龙骨牡蛎汤(CHLM)对心肌梗死合并焦虑大鼠肠道屏障、内毒素(lipopolysaccharides,LPS)/核因子κB(nuclear transcription factor-κB,NF-κB)介导的心肌炎性损伤、心脏收缩功能、行为学、血清炎症因子的影响。方法将24只雄性SD大鼠随机分为假手术组、模型组、中药组。其中模型组,中药组接受为期3周的焦虑造模,在第2周末模型组及中药组进行心梗造模。假手术组正常饮水,仅挂线,不结扎。术后第二天,中药组予柴胡加龙骨牡蛎汤13.6 g/kg灌胃。模型组及假手术组予等体积生理盐水灌胃。检测大鼠垂直运动分数、水平运动分数、开放臂进入次数百分比(the percentage of open arm entry,OE%)、开放臂进入时间百分比(the percentage of open arm time,OT%)等行为学指标,检测大鼠左室射血分数(left ventricular injection fraction,LVEF)、左室缩短分数(left ventricular systolic function,LVFS)、左心室舒张末期内径(left ventricular internal diameter at end-diastole,LVIDd)和左心室收缩末期内径(left ventricular internal diameter at end-systole,LVIDs)等超声指标。对心脏组织石蜡切片进行苏木精—伊红(hematoxylin-eosin,HE)染色后观察。用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)测定血清LPS及炎性因子水平,用蛋白免疫印迹法(Western-blot,WB)检测心肌组织NF-κB信号通路相关蛋白表达。结果(1)取样前,假手术组7只大鼠存活,模型组,中药组各6只大鼠存活。(2)肠道屏障指标:与模型组相比,中药组闭合蛋白(occludin)、闭锁连接蛋白-1(zonula occludens-1,ZO-1)表达升高,差异具有显著统计学意义。中药组紧密连接蛋白-1(claudin-1)表达相对模型组有升高趋势,但差异无统计学意义。(3)NF-κB相关蛋白:与模型组相比,中药组NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、磷酸化的核因子κB p65与核因子κB p65的比值(ratio of NF-κB pp65 to NF-κB p65,NF-κB pp65/p65)、白细胞介素1β(interleukin-1β,IL-1β)表达下调具有显著统计学意义。核因子κB抑制蛋白α(inhibitory subunit of NF-κB alpha,IκBα)表达上调具有统计学意义。(4)行为学指标:与模型组相比,中药组OE%、OT%、垂直运动评分、水平运动评分升高且具有统计学意义;(5)心功能指标:与模型组相比,中药组LVEF、LVFS升高且均具有统计学意义,LVIDs降低且具有统计学意义,LVIDd有下降趋势,但无统计学差异。(6)血清学指标:与模型组相比,中药组LPS、IL-1β、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)下降具有统计学意义,白细胞介素6(interleukin-6,IL-6)下降具有显著统计学意义。结论柴胡加龙骨牡蛎汤能够改善心肌梗死合并焦虑模型大鼠的肠道屏障损伤、心肌炎性损伤,增强左室收缩功能,减轻焦虑行为,其机制可能与肠道屏障及LPS/NF-κB信号介导的炎症反应相关。
文摘OBJECTIVE:To evaluated the effectiveness and safety of Chinese herbal medicines(CHMs)for coronary heart disease(CHD)complicated with anxiety.METHODS:Randomized controlled clinical trials(RCTs)with parallel-groups were included after searching through electric-databases from inception to May,2017.Meta-analysis was undertaken with Rev Man 5.3 software.RESULTS:Twenty-three RCTs enrolling 1654 patients were included in this systematic review.The combination therapy(CHMs combined with anxiolytic)appeared to be superior to anxiolytic in terms of reducing the score of Zung Self-rating Anxiety scale(SAS)(mean Difference(MD),-12.25;95%confidence interval(CI),-14.01 to-10.48,eliminating method;MD,-3.92;95%CI,-5.48 to-2.35,tranquilizing method),improving the total effect rate(relative risk(RR),1.26;95%CI,1.08 to 1.46,eliminating method)and reducing the TCM symptoms scores(MD,-2.24;95%CI,-4.25 to-0.23,tranquilizing method)with a lower incidence of adverse events(RR,0.46;95%CI,0.25 to 0.85,tonifying method).CHMs demonstrated benefits in lowering the score of Hamilton Anxiety Rating scale(MD,-6.77;95%CI,-8.16 to-5.37,tonifying method),lowering the score of SAS(MD,-10.1;95%CI,-13.73 to-6.30,tonifying method)and reducing the TCM symptoms scores(MD,-2.18;95%CI,-3.12 to-1.24,tranquilizing method).CONCLUSION:We got a low evidence that CHMs,which had less side effects,showed potentially benefits to patients with CHD complicated with anxiety.While the results should be interpreted with caution.Trails with higher quality are required to verify the effectiveness and safety of CHMs for CHD complicated with anxiety.
