脂氧素A4对肝细胞生长因子诱导HepG2肝癌细胞血管生成相关细胞因子表达的影响  

Effects of lipoxin A4 on hepatocyte growth factor-induced angiogenesis-related cytokines in HepG2 cells

作　　者：周晓燕[1,2] 王红梅[1] 蔡震宇[1] 徐方云[1] 黄永红[1] 朱俊[1] 吴萍[2] 叶笃筠[2] 

机构地区：[1]南昌大学医学院病理生理系,江西南昌330006 [2]华中科技大学同济医学院病理生理系,湖北武汉430030

出　　处：《中国病理生理杂志》2011年第2期300-303,共4页Chinese Journal of Pathophysiology

摘　　要：目的:探讨脂氧素A4(LXA4)对肝细胞生长因子(HGF)诱导的HepG2肝癌细胞血管生成相关细胞因子表达的影响。方法:体外培养HepG2肝癌细胞,实验分为空白组、HGF处理组、HGF+LXA4处理组、HGF+脂氧素受体激动剂BML-111处理组。RT-PCR检测脂氧素受体(ALX)表达情况,Western blotting检测COX-2、MMP-2、MMP-9、IκBα和NF-κB p65的表达量,ELISA检测TNF-α、IL-1β、VEGF和TGF-β分泌水平,荧光素酶报告质粒检测NF-κB转录活性。结果:HepG2肝癌细胞表达ALX,LXA4和BML-111下调COX-2、MMP-2和MMP-9,抑制TNF-α、IL-1β、VEGF和TGF-β分泌,并且干扰NF-κB转位及其转录活性。结论:脂氧素抑制HGF诱导HepG2肝癌细胞表达血管生成相关细胞因子,包括VEGF、COX-2、TNF-α、IL-1β、TGF-β、MMP-2及MMP-9,此效应可能通过干扰NF-κB活化实现。AIM： To explore the possibility that lipoxin A4 （LXA4 ） regulates the expression of angiogenesis - related eytokines in HepG2 cells induced by hepatocyte growth factor（HGF）. METHODS： The HepG2 cells were divided into control group, HGF treatment group, HGF ＋ LXA4 treatment group and HGF ＋ BML - 111 （ an agonist of lipoxin A4 receptor） treatment group. The expression of lipoxin A4 receptor in HepG2 cells was measured by RT - PCR. The protein levels of COX - 2, MMP - 2, MMP - 9, IκBα and NF - KB p65 in the cells were determined by Western blotting. The release of TNF - α, IL - 113, VEGF and TGF - 13 in the supematants of the cell culture was examined by ELISA. The activi- ty of NF - κB transcription in HepG2 cells was tested by transfection and luciferase activity assay. RESULTS： The expres- sion of lipoxin A4 receptor was detected in HepG2 cells. LXA4 and BML - 111 were able to down - regulate HGF - induced production of COX - 2, MMP - 2 and MMP - 9. The secretion of TNF - α, IL - 1β, VEGF and TGF - β was also de- creased. Furthermore, LXA4 and BML - 111 restrained HGF - induced IκBα degradation, NF - κB translocation, and the transcriptional activity of NF - KB in HepG2 cells. CONCLUSION： LXA4 is able to inhibit HGF - induced angiogenesis - related cytokines, including VEGF, COX - 2, TNF - a, IL - 1β, TGF - β, MMP - 2 and MMP - 9, by inhibition of NF - KB activation.

关 键 词：脂氧素 血管生成 细胞因子类 

分 类 号：R364.5[医药卫生—病理学]