李显东　吕军　胡秀学

[摘要] 目的 研究L-精氨酸、不對称二甲基精氨酸（ADMA）和对称性二甲基精氨酸（SDMA）3种生物标志物来预测川崎病（KD）患儿的预后。 方法 选取2012年1月～2013年12月湖北省十堰市太和医院儿科住院的典型KD患儿39例作为病例组，采集静脉血，同时收集与之年龄相匹配的呼吸道感染伴有发热并排除了心肌受累患儿27例的静脉血浆作为对照组，测量病例组和对照组中L-精氨酸、ADMA和SDMA的血浆水平。 结果 静脉注射免疫球蛋白（IVIG）治疗前病例组KD1患儿的血浆L-精氨酸、ADMA和SDMA水平均低于对照组（P < 0.05或P < 0.01）。IVIG治疗后病例组不同治疗时间患儿的L-精氨酸、ADMA、L-精氨酸/ADMA比率（AAR）和精氨酸甲基化综合指数（AMI）比较，差异有高度统计学意义（P < 0.01）。病例组KD1、病例组KD2、病例组KD3、病例组KD4患儿血浆SDMA水平均低于对照组（P < 0.01），但IVIG治疗前后的比较，差异无统计学意义（P > 0.05）；病例组KD2、病例组KD3和病例组KD4患儿的AMDA/SMDA比率（ASR）均高于对照组与病例组KD1患儿（P < 0.01）。在病例组KD1患儿中，冠脉扩张患儿L-精氨酸水平高于无冠脉扩张患儿（P < 0.01）；在病例组KD2患儿及病例组KD3患儿中，冠脉扩张患儿L-精氨酸水平均低于无冠脉扩张患儿（P < 0.01）。 结论 L-精氨酸、ADMA和SDMA的水平可能与KD有关。低水平L-精氨酸及IVIG治疗后ASR与冠状动脉异常的KD患儿有关。

[关键词] 不对称二甲基精氨酸；对称性二甲基精氨酸；川崎病；L-精氨酸

[中图分类号] R5414.1 [文献标识码] A [文章编号] 1673-7210（2018）04（b）-0063-04

[Abstract] Objective To study the three biomarkers of L-arginine， asymmetric dimethylarginine （ADMA） and symmetric dimethylarginine （SDMA） are used to predict the prognosis of children patients with kawasaki disease （KD）. Methods From January 2012 to December 2013， 39 children with KD in Department of Pediatric in Taihe Hospital were selected as the case group， venous blood was collected， and at the same time， the plasma of 27 children patients matched with age was collected as control group， which of respiratory infection was accompanied by fever and exclusion of involvement of myocardium. The plasma levels of L-arginine， ADMA and SDMA were measured in the case group and control group. Results The plasma levels of L-arginine， ADMA and SDMA before intravenous immunoglobulin （IVIG） treatment of children in the case group KD1 were lower than those of control group （P < 0.05 or P < 0.01）. After IVIG treatment， the L-arginine， ADMA， L-arginine/ADMA ratio （AAR） and arginine methylation composite index （AMI） of different treatment time in case group were compared， the differences were highly statistically significant （P < 0.01）. The plasma levels of SDMA of children in case group KD1， case group KD2， case group KD3， case group KD4 were all lower than the control group （P < 0.01）， but comparison of before and after IVIG treatment， the difference were not statistically significant （P > 0.05）. The AMDA/SMDA ratio （ASR） of children in case group KD2， case group KD3， case group KD4 were all higher than control group and case group KD1 （P < 0.01）. In the case group KD1， the L-arginine level of children with coronary artery dilation was higher than that in children without coronary artery dilatation （P < 0.01）， while in the case group KD2 and the case group KD3， the children patients with coronary artery dilation was lower than that in children without coronary artery dilatation （P < 0.01）. Conclusion The levels of L-arginine， ADMA and SDMA may be related to KD. Low level of L-arginine and ASR of after IVIG treatment are associated with children patients with abnormal coronary artery KD.

[Key words] Asymmetric dimethylarginine； Symmetric dimethylarginine； Kawasaki diseas； L- arginine

川崎病（kawasaki disease，KD）是一种以全身血管炎变为主要病理的急性发热性出疹性小儿疾病[1]。1967年日本川崎富作医生首次报道，本病可发生严重心血管病变，如动脉瘤、心肌炎、缺血性心脏病等而致死[2]。研究发现，内皮功能障碍（ED）是KD重要的病理基础[3]。内皮细胞产生的一氧化氮（nitric oxide，NO）作用于平滑肌细胞从而扩张血管，NO缺乏对ED疾病发生发展具有重要的促进作用。研究发现急性KD患儿NO代谢物NOx（亚硝酸盐+硝酸盐）浓度增加，血浆硝酸盐浓度在KD急性期和亚急性期增加[4]。不对称二甲基精氨酸（asymmetric dimethylarginine，ADMA）是一氧化氮合酶（NOS）的内源性抑制剂，ADMA通过与NOS的底物L-精氨酸竞争，抑制NO生成[5-6]。因此，血浆L-精氨酸/ADMA比率（AAR）可作为NO生物利用度的指标[6]。研究表明，ADMA/对称二甲基精氨酸（symmetric dimethylarginine，SDMA）的比例可作为二甲基精氨酸二甲基氨基水解酶（DDAH）的活性的间接指标，有助于了解疾病的发病机制[7]。……