EOFAZ抑制TNF-α诱导的血管新生和炎症损伤  

EOFAZ inhibited angiogenesis and inflammatory injury induced by TNF-α

作　　者：付凌云 杨红 林丹 黄妮雯 徐旖旎 陶玲 沈祥春 FU Ling-yun;YANG Hong;LIN Dan;HUANG Ni-wen;XU Yi-ni;TAO Ling;SHEN Xiang-chun(High Educational Key Lab of Guizhou Province for Natural Medicinal Pharmacology and Druggability,Guizhou Medical University,Guizhou 550025,China;State Key Lab of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guizhou 550025,China;High Educational Key Lab of Guizhou Province for Natural Medicinal Pharmacology and Drugability,Guizhou Medical University,Guizhou 550025,China;Key Lab of Guiyang City for Natural Medicinal Pharmacology and Drugability,School of Pharmaceutical Sciences,Guizhou Medical University,Guizhou 550025,China)

机构地区：[1]贵州医科大学药学院天然药物资源优效利用重点实验室,贵州贵阳550025 [2]贵州医科大学药学院药用植物功效与利用国家重点实验室,贵州贵阳550025 [3]贵州医科大学药学院贵州省普通高等学校天然药物药理与成药性评价重点实验室,贵州贵阳550025 [4]贵州医科大学药学院贵州省特色天然药物资源高效利用工程中心,贵州贵阳550025

出　　处：《中国药理学通报》2018年第11期1594-1599,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81360650;81760725);贵州省科技创新团队项目(黔科合人才团队[2015]4025号);贵州省高层次创新型人才百层次人才项目(贵州省科技厅黔科合人才[2015]4029号);贵阳市科技基金项目(筑科合同[20151001]药07号)

摘　　要：目的研究艳山姜挥发油(essential oil of Fructus Alpiniae zerumbet,EOFAZ)对肿瘤坏死因子α(tumor necrosis factorα,TNF-α)诱导内皮细胞血管新生及炎性损伤的作用,以及作用机制。方法分别建立TNF-α诱导的体外内皮细胞血管新生及体内小鼠胸主动脉炎性损伤模型。采用体外血管新生小管成环实验,分析TNF-α诱导HUVECs的血管新生;Western blot和qRT-PCR实验法分别检测HUVECs中VEGFR-2蛋白和mRNA的表达;ELISA法检测小鼠血清中VEGFR-2的分泌水平;采用HE染色分析小鼠胸主动脉炎性损伤。结果 EOFAZ和ERK抑制剂U0126明显抑制TNF-α诱导的HUVECs血管新生小管成环数量(P<0.01);EOFAZ能够下调TNF-α诱导小鼠血清中VEGFR-2的分泌(P<0.01);EOFAZ和U0126对TNF-α诱导的HUVECs中VEGFR-2的蛋白和mRNA表达有抑制作用(P<0.01);EOFAZ能够抑制TNF-α诱导小鼠胸主动脉炎性细胞的浸润。结论 EOFAZ能抑制TNF-α诱导血管新生和炎性损伤,其机制与通过ERK信号通路下调VEGFR-2的表达有关。Aim To investigate the effects of essential oil of Fructus Alpiniae zerumbet(EOFAZ)on angiogenesis and inflammatory injury induced by tumor necrosis factor-α(TNF-α)and the underlying mechanisms.Methods Human umbilical vein endothelial cells(HUVECs)angiogenesis model in vitro and mice thoracic aorta inflammatory injury model in vivo were established by TNF-α,respectively.Angiogenesis assay was used to investigate the effects of EOFAZ on the tube formation of HUVECs angiogenesis.Western blot and qRT-PCR were used to detect the protein and mRNA expressions of VEGFR-2 in HUVECs,respectively.The secrection level of VEGFR-2 in serum of mice was detected by ELISA,and HE staining assay was performed on inflammatory injury in thoracic aorta of mice.Results EOFAZ and ERK inhibitor U0126 significantly inhibited the tube formation of HUVECs angiogenesis(P<0.01),EOFAZ down-regulated the secretion level of VEGFR-2 in TNF-α-induced mice(P<0.01),EOFAZ and U0126 suppressed the protein and mRNA expression of VEGFR-2 in TNF-α-induced HUVECs(P<0.01),and EOFAZ inhibited inflammatory cells infiltration in thoracic aorta of TNF-α-induced mice.Conclusions EOFAZ significantly inhibits angiogenesis and inflammatory injury induced by TNF-α,the mechanism of the inhibitory effect of EOFAZ may be related to down-regulating the expression of VEGFR-2 via ERK signaling pathway.

关 键 词：艳山姜挥发油 人脐静脉内皮细胞 肿瘤坏死因子Α 细胞外信号调节激酶 血管新生 炎症 血管内皮细胞生长因子受体-2 

分 类 号：R284.1[医药卫生—中药学] R322.12[医药卫生—中医学]