BACKGROUND Lung cancer(LC)combined with chronic obstructive pulmonary disease(COPD)is a common combination of comorbidities.Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induce...BACKGROUND Lung cancer(LC)combined with chronic obstructive pulmonary disease(COPD)is a common combination of comorbidities.Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC,and are also crucial to the treatment of LC combined with COPD.Modern studies have shown that Tao Hong Si Wu Tang(THSW)has vasodilatory,anti-inflammatory,anti-fatigue,anti-shock,immunoregulatory,lipid-reducing,micronutrient-supplementing,and anti-allergy effects.AIM To observe the effects of THSW on COPD and LC in mice.METHODS A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups:Blank control group(group A),model control group(group B),THSW group(group C),IL-6 group(group D),and THSW+IL-6 group(group E),with 20 mice in each group.A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip,and an LC model was replicated by in situ inoculation using the Lewis cell method.RESULTS The blank control group exhibited a clear alveolar structure.The model control and IL-6 groups had thickened alveolar walls,with smaller alveolar lumens,interstitial edema,and several inflammatory infiltrating cells.Histopathological changes in the lungs of the THSW and THSW+IL-6 groups were less than those of the model control group.The serum IL-1β,IL-6,and TNF-αlevels and IL-6R,JAK,p-JAK,STAT1/3,p-STAT1/3,FOXO,p-FOXO,and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group(P<0.01).Compared with the model control group,the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues(P<0.01),and the THSW group had significantly higher serum IL-1β,IL-6,and TNF-αlevels and IL-7R expression levels in lung tissues(P<0.01)but significantly decreased IL-6R,JAK,p-JAK,STAT1/3,p-STAT1/3,FOXO,p-FOXO,and IL-7R levels(P<0.01).CONCLUSION THSW reduces the serum IL-1β,IL-6,and TNF-αlevels in the mouse model with anti-inflammatory effects.Its antiinflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.展开更多
目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照...目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。展开更多
基金Supported by Liaoning Province“Xingliao Talent Program”Project,No.XLYC2007019.
文摘BACKGROUND Lung cancer(LC)combined with chronic obstructive pulmonary disease(COPD)is a common combination of comorbidities.Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC,and are also crucial to the treatment of LC combined with COPD.Modern studies have shown that Tao Hong Si Wu Tang(THSW)has vasodilatory,anti-inflammatory,anti-fatigue,anti-shock,immunoregulatory,lipid-reducing,micronutrient-supplementing,and anti-allergy effects.AIM To observe the effects of THSW on COPD and LC in mice.METHODS A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups:Blank control group(group A),model control group(group B),THSW group(group C),IL-6 group(group D),and THSW+IL-6 group(group E),with 20 mice in each group.A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip,and an LC model was replicated by in situ inoculation using the Lewis cell method.RESULTS The blank control group exhibited a clear alveolar structure.The model control and IL-6 groups had thickened alveolar walls,with smaller alveolar lumens,interstitial edema,and several inflammatory infiltrating cells.Histopathological changes in the lungs of the THSW and THSW+IL-6 groups were less than those of the model control group.The serum IL-1β,IL-6,and TNF-αlevels and IL-6R,JAK,p-JAK,STAT1/3,p-STAT1/3,FOXO,p-FOXO,and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group(P<0.01).Compared with the model control group,the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues(P<0.01),and the THSW group had significantly higher serum IL-1β,IL-6,and TNF-αlevels and IL-7R expression levels in lung tissues(P<0.01)but significantly decreased IL-6R,JAK,p-JAK,STAT1/3,p-STAT1/3,FOXO,p-FOXO,and IL-7R levels(P<0.01).CONCLUSION THSW reduces the serum IL-1β,IL-6,and TNF-αlevels in the mouse model with anti-inflammatory effects.Its antiinflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.
文摘目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。
