川崎病患儿血清酸性鞘磷脂酶、钙调神经磷酸酶水平和炎症因子表达的相关性以及与免疫球蛋白治疗效果的关系研究

目的　探讨川崎病（kawasaki disease，KD）患儿血清酸性鞘磷脂酶（acid sphingomyelinase，ASM）、钙调神经磷酸酶（calcineurin，CaN）水平和炎症因子表达的相关性以及与免疫球蛋白治疗效果的关系研究。方法　选择2017年2 月～ 2020 年3 月邯郸市中心医院收治的196 例KD 患儿（KD 组）和198 例健康体检儿童（对照组）为研究对象。检测所有儿童血清ASM，CaN 及炎症因子 白细胞介素（interleukin ，IL）-2，C 反应蛋白（C-reactive protein，CRP），白细胞介素（interleukin ，IL）-6，肿瘤坏死因子（tumor necrosis factor，TNF）-α] 水平。分析血清ASM，CaN 水平与IL-2，CRP，IL-6，TNF-α 的相关性。根据静脉注射免疫球蛋白（intravenous immunoglobulin，IVIG）治疗反应性将KD 患儿分为IVIG 反应组（n=165）和IVIG 无反应组（n=31），分析IVIG 治疗效果的影响因素。结果　KD组患儿血清ASM（3.31±0.75nmol/L），CaN（2.52±0.62ng/ml），IL-2（3.65±0.95pg/ml），CRP（31.15±5.34mg/L），IL-6（85.91±19.75pg/ml），TNF-α（5.19±0.98μg/L）水平均高于对照组（1.05±0.31nmol/L，0.86±0.25ng/ml，0.95±0.23pg/ml，1.32±0.27mg/L，23.15±6.59pg/ml，2.01±0.34μg/L）, 差异有统计学意义（t=33.715 ～ 41.914，均P ＜ 0.05）。Pearson 相关性分析结果显示:血清ASM，CaN 水平与IL-2，CRP，IL-6，TNF-α 水平均呈正相关（rASM=0.396 ～ 0.521，rCaN=0.342 ～ 0.512，均P ＜ 0.05）。单因素分析结果显示:IVIG 反应组血清ASM，CaN，CRP 和IL-6 水平以及发热时间、中性粒细胞比例和白细胞计数均低于IVIG 无反应组，差异有统计学意义（t=5.969 ～ 18.252，均P ＜ 0.05）。多因素Logistic 回归分析结果显示:ASM（OR=1.390，95%CI=1.158 ～ 1.669），CaN（OR=1.749，95%CI=1.346 ～ 2.272）和CRP（OR=1.865，95%CI=1.358 ～ 2.561）均是KD 患儿IVIG 治疗效果的影响因素（均P ＜ 0.05）。结论　KD 患儿血清ASM 和CaN 水平均异常升高，且血清ASM 和CaN 水平升高与机体发生炎症反应、IVIG 治疗无反应有关，检测血清ASM 和CaN 水平有助于评估KD 病情和IVIG 疗效。

Correlation between Serum Acid Sphingomyelinase,Calcineurin Levels and Expression of Inflammatory Factors in Children with Kawasaki Disease and the Relationship with the Therapeutic Effect of Immunoglobulin

Objective　To investigate the correlation between serum acid sphingomyelinase (ASM), calcineurin(CAN) levels and expression of inflammatory factors in children with Kawasaki disease(KD) and the relationship with the therapeutic effect of immunoglobulin. Methods　196 children with KD (KD group) who were treated in Handan Central Hospital from February 2017 to March 2020 and 198 healthy children (control group) were selected as the study subjects. The levels of serum ASM, CaN and inflammatory factorsinterleukin (IL)-2, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α] were detected in all children. The correlation of serum ASM and CaN levels with IL-2, CRP, IL-6 and TNF-α were analyzed. According to intravenous immunoglobulin therapy (IVIG) treatment response, children with KD were divided into IVIG response group (n=165 ) and IVIG non-response group (n=31) treatment response. The influencing factors of IVIG treatment effect were analyzed. Results　The levels of serum ASM（3.21±0.75nmol/L）, CaN（2.52±0.62ng/ml）, IL-2（3.65±0.95pg/ml）, CRP（31.15±5.34mg/L）, IL-6（85.91±19.75pg/ml）and TNF-α（5.19±0.98μg/L）in KD group were higher than those i n cont r o l g r o up（1. 0 5 ± 0 .31nmol /L， 0 .86± 0 .25ng/ml ，0. 9 5 ± 0 .23pg/ml ， 1 .32± 0 .27mg /L，23.15±6.59pg/ml，2.01±0.34μg/L）, the differences were statistically significant（t=33.715 ～ 41.914，all P ＜ 0.05）. Pearson correlation analysis showed that serum ASM and CaN levels were positively correlated with IL-2, CRP, IL-6 and TNF-α levels（rASM=0.396 ～ 0.521，rCaN=0.342 ～ 0.512，all P ＜ 0.05）. Univariate analysis showed that the levels of serum ASM, CAN, CRP, IL-6 levels, heating time, neutrophil proportion and white blood cell count in IVIG response group were lower than those in IVIG non-response group，the differences were statistically significant（t=5.969 ～ 18.252，all P ＜ 0.05）. Multivariate Logistic regression analysis showed that ASM（OR=1.390，95%CI=1.158 ～ 1.669），CaN（OR=1.749， 95%CI=1.346 ～ 2.272）and CRP（OR=1.865，95%CI=1.358 ～ 2.561）were the influencing factors of IVIG treatment effectin children with KD (all P<0.05). Conclusion　The serum ASM and CaN levels in children with KD were abnormally increased, and the increase of serum ASM and CaN levels were related to the inflammatory reaction in the body and the nonresponse to IVIG treatment. The detection of serum ASM and CaN levels is helpful to evaluate the disease of KD and the efficacy of IVIG.