目的通过检测口腔癌皮下移植瘤小鼠小肠中代谢物和代谢通路的变化,分析过表达miR-181a-5p对皮下移植瘤小鼠小肠中代谢物和代谢物组的影响。方法实验分为3组,空白对照(Control)组、阴性对照(negative control,NC)组以及实验(over express...目的通过检测口腔癌皮下移植瘤小鼠小肠中代谢物和代谢通路的变化,分析过表达miR-181a-5p对皮下移植瘤小鼠小肠中代谢物和代谢物组的影响。方法实验分为3组,空白对照(Control)组、阴性对照(negative control,NC)组以及实验(over expression of miR-181a-5p,OE)组。将不同组别处理后的细胞混悬液,通过皮下注射到M-NSG重度免疫缺陷雌性小鼠右侧腹股沟中上部,构建成口腔癌皮下移植瘤小鼠模型。按时记录小鼠体重变化,对小鼠小肠组织进行HE染色,观察各组病理变化。采用超高效液相色谱-串联飞行时间质谱联用仪和串联Orbitrap质谱联用仪检测NC组、OE组和Control组小鼠小肠中的代谢物,使用XCMS预分析原始数据,质量评价样本数据,鉴定Control组与NC组、NC组与OE组的差异代谢物,进行KEGG富集分析获取差异代谢通路。结果Control组和NC组小肠组织中共鉴定出170种差异代谢物。代谢物富集的显著性信号通路包括胆碱代谢、丙氨酸、天冬氨酸和谷氨酸代谢、γ-氨基丁酸(GABA)神经突触代谢、甘油磷脂代谢、环磷酸腺苷(cAMP)信号通路代谢、癌症中心碳代谢以及烟酸和烟碱胺代谢通路。NC组和OE组相比,小鼠小肠中检测到VIP(variable importance in the projection)>2的差异代谢物有16种,显著性差异代谢物包括甘油磷酰胆碱、棕榈酸、3-羟基丁酰肉碱、β-羟丁酸等。代谢物富集到的显著性差异通路为胆碱代谢通路。结论口腔癌皮下移植瘤可引起小鼠小肠的代谢物发生变化,主要改变了小肠中与能量代谢相关的代谢物。过表达miR-181a-5p影响口腔癌皮下移植瘤小鼠小肠代谢物,代谢物富集通路为胆碱代谢通路。展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
文摘目的通过检测口腔癌皮下移植瘤小鼠小肠中代谢物和代谢通路的变化,分析过表达miR-181a-5p对皮下移植瘤小鼠小肠中代谢物和代谢物组的影响。方法实验分为3组,空白对照(Control)组、阴性对照(negative control,NC)组以及实验(over expression of miR-181a-5p,OE)组。将不同组别处理后的细胞混悬液,通过皮下注射到M-NSG重度免疫缺陷雌性小鼠右侧腹股沟中上部,构建成口腔癌皮下移植瘤小鼠模型。按时记录小鼠体重变化,对小鼠小肠组织进行HE染色,观察各组病理变化。采用超高效液相色谱-串联飞行时间质谱联用仪和串联Orbitrap质谱联用仪检测NC组、OE组和Control组小鼠小肠中的代谢物,使用XCMS预分析原始数据,质量评价样本数据,鉴定Control组与NC组、NC组与OE组的差异代谢物,进行KEGG富集分析获取差异代谢通路。结果Control组和NC组小肠组织中共鉴定出170种差异代谢物。代谢物富集的显著性信号通路包括胆碱代谢、丙氨酸、天冬氨酸和谷氨酸代谢、γ-氨基丁酸(GABA)神经突触代谢、甘油磷脂代谢、环磷酸腺苷(cAMP)信号通路代谢、癌症中心碳代谢以及烟酸和烟碱胺代谢通路。NC组和OE组相比,小鼠小肠中检测到VIP(variable importance in the projection)>2的差异代谢物有16种,显著性差异代谢物包括甘油磷酰胆碱、棕榈酸、3-羟基丁酰肉碱、β-羟丁酸等。代谢物富集到的显著性差异通路为胆碱代谢通路。结论口腔癌皮下移植瘤可引起小鼠小肠的代谢物发生变化,主要改变了小肠中与能量代谢相关的代谢物。过表达miR-181a-5p影响口腔癌皮下移植瘤小鼠小肠代谢物,代谢物富集通路为胆碱代谢通路。
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
