目的探讨九味白术汤对溃疡性结肠炎(UC)大鼠肠黏膜免疫屏障及微小RNA(miR)-155/细胞因子信号转导抑制因子-1(SOCS-1)轴的影响。方法将大鼠随机分为对照组、模型组、药物组、药物+阴性对照组、药物+miR-155过表达组,每组8只,以2,4,6-三...目的探讨九味白术汤对溃疡性结肠炎(UC)大鼠肠黏膜免疫屏障及微小RNA(miR)-155/细胞因子信号转导抑制因子-1(SOCS-1)轴的影响。方法将大鼠随机分为对照组、模型组、药物组、药物+阴性对照组、药物+miR-155过表达组,每组8只,以2,4,6-三硝基苯磺酸(TNBS)诱导建立UC模型,给药7 d后,检测疾病活动指数(DAI)评分,HE染色观察结肠黏膜组织形态变化,ELISA法检测结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,RT-qPCR法检测结肠黏膜组织miR-155表达,Western blot法检测结肠黏膜组织SOCS-1、GP130、iNOS、RORγt、STAT3蛋白表达。结果与对照组比较,模型组大鼠1、2、3、4、5、6、7 d DAI评分升高(P<0.05);与模型组比较,药物组大鼠5、6、7 d DAI评分降低(P<0.05)。与对照组比较,模型组大鼠结肠黏膜损伤评分,结肠黏膜组织病理学评分,结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,miR-155表达,GP130、iNOS、RORγt、STAT3蛋白表达均升高(P<0.05),SOCS-1蛋白表达降低(P<0.05);与模型组比较,药物组、药物+阴性对照组大鼠结肠黏膜损伤评分,结肠黏膜组织病理学评分,结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,miR-155表达,GP130、iNOS、RORγt、STAT3蛋白表达均降低(P<0.05),SOCS-1蛋白表达升高(P<0.05)。结论九味白术汤对UC大鼠肠黏膜免疫屏障具有保护作用,该作用可能与抑制miR-155表达从而促进SOCS-1表达有关。展开更多
Although microRNA-155(miR-155)is considered a pro-inflammatory mediator,cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells.In this study,we identified the drama...Although microRNA-155(miR-155)is considered a pro-inflammatory mediator,cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells.In this study,we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide(LPS)stimulation;223 genes were down-regulated and 85 genes were up-regulated,including suppressor of cytokine signaling 1(SOCS1)and transforming growth factor-β-activated kinase 1-binding protein 2(TAB2),two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4(TLR4)signaling pathway.We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation,and as a proinflammatory mediator by down-regulating SOCS1 in the later stage.Meanwhile,overexpression of TAB23'untranslated region(UTR)in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155,which resulted in an elevated expression level of SOCS1 protein.These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.展开更多
文摘目的探讨九味白术汤对溃疡性结肠炎(UC)大鼠肠黏膜免疫屏障及微小RNA(miR)-155/细胞因子信号转导抑制因子-1(SOCS-1)轴的影响。方法将大鼠随机分为对照组、模型组、药物组、药物+阴性对照组、药物+miR-155过表达组,每组8只,以2,4,6-三硝基苯磺酸(TNBS)诱导建立UC模型,给药7 d后,检测疾病活动指数(DAI)评分,HE染色观察结肠黏膜组织形态变化,ELISA法检测结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,RT-qPCR法检测结肠黏膜组织miR-155表达,Western blot法检测结肠黏膜组织SOCS-1、GP130、iNOS、RORγt、STAT3蛋白表达。结果与对照组比较,模型组大鼠1、2、3、4、5、6、7 d DAI评分升高(P<0.05);与模型组比较,药物组大鼠5、6、7 d DAI评分降低(P<0.05)。与对照组比较,模型组大鼠结肠黏膜损伤评分,结肠黏膜组织病理学评分,结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,miR-155表达,GP130、iNOS、RORγt、STAT3蛋白表达均升高(P<0.05),SOCS-1蛋白表达降低(P<0.05);与模型组比较,药物组、药物+阴性对照组大鼠结肠黏膜损伤评分,结肠黏膜组织病理学评分,结肠黏膜组织TNF-α、IL-23、IL-6、IL-1β水平,miR-155表达,GP130、iNOS、RORγt、STAT3蛋白表达均降低(P<0.05),SOCS-1蛋白表达升高(P<0.05)。结论九味白术汤对UC大鼠肠黏膜免疫屏障具有保护作用,该作用可能与抑制miR-155表达从而促进SOCS-1表达有关。
基金the National Natural Science Foundation of China(Nos.81701568,81930041,81571524,81872248,and 91842103)the Zhejiang Provincial Natural Science Foundation of China(Nos.Y15C080001 and Z19H100001)the Zhejiang Provincial Key Laboratory for Immunity and Inflammatory Diseases for its support。
文摘Although microRNA-155(miR-155)is considered a pro-inflammatory mediator,cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells.In this study,we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide(LPS)stimulation;223 genes were down-regulated and 85 genes were up-regulated,including suppressor of cytokine signaling 1(SOCS1)and transforming growth factor-β-activated kinase 1-binding protein 2(TAB2),two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4(TLR4)signaling pathway.We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation,and as a proinflammatory mediator by down-regulating SOCS1 in the later stage.Meanwhile,overexpression of TAB23'untranslated region(UTR)in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155,which resulted in an elevated expression level of SOCS1 protein.These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.
