川崎病急性期血清对血管内皮细胞MMP-3和TNF—α表达的影响及丙种球蛋白的干预作用  

Effect of γ-globulin on the expression of MMP-3 and TNF-α in human umbilical vein endothelial cells induced by serum from children with Kawasaki disease

作　　者：张园海[1] 何跃娥[1] 项如莲[1] 吴蓉洲[1] 徐强[1] 荣星[1] 陈其[1] 

机构地区：[1]温州医学院附属育英儿童医院小儿心内科,325027

出　　处：《浙江医学》2009年第4期451-453,465,共4页Zhejiang Medical Journal

摘　　要：目的观察川崎病（KD）患儿急性期血清对脐静脉内皮细胞（HUVEC）表达基质金属蛋白酶-3（MMP-3）和肿瘤坏死因子-α（TNF—α）的影响及人血丙种球蛋白（IVIG）对上述过程的调节作用。方法分别采集30例KD急性期患儿（冠脉正常15例，冠脉损害15例）、10例发热患儿和10例正常健康儿童静脉血3ml，常规分离血清待用。HUVEC培养分为正常血清组（C组）、发热血清组（F组）、KD冠脉无损害血清组（NAC组）、KD冠脉无损害血清＋IVIG组（NACI组）、KD冠脉损害血清＋IVIG组（ACI组）、KD冠脉损害血清组（AC组）。每组分别培养12h后吸取上清液，应用ELISA法测定细胞上清液MMP-3、TNF—α水平。结果经KD患儿血清作用后的HUVEC培养上清液中MMP-3、TNF-α水平升高明显，与C组、F组相比差异有统计学意义（均P〈0．01），其中AC组更高，与NAC组相比差异有统计学意义（P〈0．01）；F组上清液活性虽然低于KD组，但仍高于C组（P〈0．05）。经IVIG干预后，AC组、NAC组MMP-3、TNF—α水平下降，差异有统计学意义均P〈0．01）。HUVEC培养上清液中MMP-3与TNF—α含量之间呈显著性正相关（r=0.923，P〈0．01）。结论KD患儿急性期血清能诱导HUVEC表达MMP-3、TNF—α增加，MMP-3、TNF—α可能参与KD患儿冠脉损害的发生发展；人血丙种球蛋白防治冠脉损害的机制，可能与抑制内皮细胞表达MMP-3、TNF—α有关。Objective To investigate the expression of MMP-3 and TNF-α in human umbilical vein endothelial cell （HUVEC） induced by the serum from children with acute phase of Kawasaki disease （KD） and the inhibitory effect of γ - globulin on the expression. Methods Serum samples were collected from 30 children with acute phase KD （15 with no coronary arterial lesions and 15 with coronary arterial lesions）, 10 children with fever and 10 normal children. HUVEC were cultured in 6 different conditional media with serum from normal children （C group）,from febrile children （F group）, from KD children with coronary artery lesion （AC group）, from KD with coronary artery lesion ＋ γ - globulin （ACI group）, from KD without coronary artery lesion （NAC group） and from KD without coronary artery lesion ＋ γ-globulin （NACI group）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the MMP-3 and TNF- α concentration in culture supernatant. Results Compared with C group and F group, MMP-3 and TNF- α concentrations in supernatant of HUVEC cultured with serum from KD patients were all significantly elevated （P〈0.01）, especially in AC group; γ -globulin significantly inhibited these elevations （P〈0.01）. The concentrations of MMP-3 in supernatant were positively correlated with those of TNF- α （r=0.923, P〈0.01）. Conclusion The expression of MMP-3 and TNF- α in human umbilical vein endothelial cells can be induced by the serum from KD patients, which might be involved in the mechanism of coronary artery lesions, γ-globulin inhibits MMP-3 and TNF-α expression in endothelial ceils, which indicates it can prevent the coronary artery lesions in KD.

关 键 词：川崎病 人血丙种球蛋白 脐静脉内皮细胞 基质金属蛋白酶-3 肿瘤坏死因子-α 

分 类 号：R725.97[医药卫生—儿科] R979.1[医药卫生—临床医学]