大剂量丙种球蛋白对川崎病肾上腺髓质素及相关基因表达的影响  

Influence of intravenous infusion of high dose gamma globulin on expression of adrenomedullin gene and related genes in children with Kawasaki disease

作　　者：张艳涛[1] 谢利剑[1] 黄敏[1] 沈捷[1] 李锦康[1] 

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院,上海200040

出　　处：《临床儿科杂志》2012年第1期84-88,共5页Journal of Clinical Pediatrics

基　　金：上海市卫生局面上课题(No.2007152);上海市科委医学引导项目(No.10411965700)

摘　　要：目的观察川崎病(Kawasaki disease,KD)患儿静脉用丙种球蛋白(IVIG)治疗前后肾上腺髓质素(adrenomedullin,ADM)及其他相关基因的表达变化,以探讨IVIG治疗KD的作用机制。方法采集40例KD患儿IVIG治疗前3 d及治疗后3 d外周血标本,男25例,女15例;发病年龄10～22个月,平均(16.7±5.4)个月;IVIG治疗方案为1 g/kg×2次。选取其中4例患儿的外周血进行芯片检测基因表达谱,聚类分析法筛选相关基因;同时选择ADM基因,对其余36例KD行ELISA法确认该基因表达变化。结果 4例KD患儿芯片分析发现,IVIG治疗后42个相关炎性基因表达下调(P<0.05)。ELISA法检测发现32例KD患儿血清ADM基因表达在IVIG治疗前明显高于治疗后(P<0.05),与芯片分析相一致;其余4例KD血清ADM浓度在治疗后明显高于治疗前(P<0.05),且均在IVIG治疗后出现冠脉扩张。结论 IVIG可能下调了急性期KD相关炎性基因表达,从而抑制冠脉损害的发生;治疗后ADM基因表达增高可能是预测KD冠脉扩张的线索之一。Objective To detect human adrenomedullin （ADM） gene and related genes mRNA and protein expression patterns in peripheral blood mononuclear cells of children with Kawasaki disease （KD）, to elucidate the mechanism of high dose intravenous infusion of gamma globulin （IVIG） for treatment of KD. Methods The blood sample was collected in 40 patients at 3 days before IVIG and at 3 clays after IVIG. Among them, 25 patients were male and 15 patients were female. The average age was （16.7 ± 5.4） months. The dose of IVIG was 1 g/kg twice a day. Four patients were randomly selected （2 were male and 2 were female） to detect gene expression pattern through microarray analysis and screen related genes by cluster analysis. The ADM gene expression was detected in other 36 patients by ELISA. Results The analysis of microarray data in 4 KD patients showed that 42 related inflammation genes were statistically down-regulated after IVIG （P 〈 0.05）. In 32 KD patients, the expression of ADM gene were significantly higher before IVIG than that after IVIG （P 〈 0.05）, which is consistent with the microarray data analysis. However, in another 4 KD patients, the expression of ADM gene were significantly lower before IVIG than that after IVIG （P 〈 0.05）. All of them had coronary artery dilation after IVIG. Conclusions It suggest that IVIG may down-regulate the expression of related inflammation genes, which inhibiting the occurrence of coronary artery damage. The up-regulated ADM expression after IVIG may be clues to predict coronary artery dilation in KD patients.

关 键 词：肾上腺髓质素 基因芯片 川崎病 儿童 

分 类 号：R725.4[医药卫生—儿科]