紫外线调节血管内皮生长因子分泌机制的研究  

Mechanism of UV-induced VEGF secretion of MEF

作　　者：李燕华[1] 毕志刚[1] 

机构地区：[1]南京医科大学第一附属医院皮肤性病科,江苏南京210029

出　　处：《临床皮肤科杂志》2006年第12期760-762,共3页Journal of Clinical Dermatology

基　　金：国家自然科学基金资助项目(30671894);江苏省重点学科基金资助项目(135-03);江苏省研究生创新基金

摘　　要：目的:探讨中波紫外线(UVB)增强血管内皮生长因子(VEGF)分泌的信号途径。方法:采用流式细胞仪检测表皮生长因子受体(EGFR)和磷酸化EGFR表达。ELISA检测上清液中VEGF水平。结果:UVB照射后15min可以检测到磷酸化EGFR表达,30min时达最高峰,1h开始下降,2～8h降至基础水平,而EGFR表达量不变。UVB(30mJ/cm2)分别照射EGFR+/-、EGFR+/+和EGFR-/-小鼠胚胎成纤维细胞(MEF),结果显示EGFR+/+MEF组VEGF分泌明显高于EGFR+/-MEF组和EGFR-/-MEF组,U-VB对EGFR-/-MEF的VEGF分泌促进作用不明显。EGFR磷酸化酶抑制因子PD153035可明显抑制VEGF分泌,1μmol/L有抑制作用,5μmol/L抑制作用增强。磷脂酰肌醇3激酶(PI3K)高度选择性抑制剂LY294002及不可逆抑制剂wortmannin均可明显抑制VEGF分泌。结论:紫外线通过EGFR-PI3K-蛋白激酶(AKT)途径增强VEGF分泌。Objective： To explore pathway of UV-induced VEGF secretion of mouse embryonic fibroblast （MEF）. Methods： Flow cytometry was used to detect the expression of total EGFR receptor and tyrosine-phosphorylated EGFR respectively. The VEGF concentration was determined by ELISA. Results： EGFR phosphorylation was detectable within 15 minutes after UV exposure. It peaked at 30 minutes, EGFR phosphorylation decreased to near basal levels between 2 and 8 hours after UV exposure. The EGFR^-/- MEF was not capable of increasing VEGF expression following UVB irradiation. In contrast, EGFR^＋/＋ MEF was strongly enhanced VEGF expression after UVB irradiation. PD153035, a selective inhibitor of EGFR tyrosine kinase activity, also inhibited the induction of VEGF protein expression i,n UVB-treated cells in a dose-dependent manner. LY294002 and wortmannin both inhibited the induction of VEGF protein expression in UVB-treated cells in a dose-dependent manner. Conclusion： UV stimulates the expression of VEGF by the way of EGFR-PI3K-AKT.

关 键 词：紫外线 中波 血管内皮生长因子 表皮生长因子受体 磷脂酰肌醇3激酶 蛋白激酶B 

分 类 号：R339.57[医药卫生—人体生理学]