摘要目的 观察左卡尼汀对肠道病毒71型(EV71)感染后手足口病(HFMD)的神经保护作用,并初步探讨其可能机制.方法 选取2015年3月至2016年7月在郑州大学附属儿童医院治疗的EV71感染后HFMD且血S100蛋白及神经元特异性烯醇化酶(NSE)异常的患儿132例,采用随机数字分组法分为常规组和左卡尼汀组,常规组(66例,男32例,女34例,中位年龄2岁2个月)予抗病毒等对症治疗,左卡尼汀组(66例,男36例,女30例,中位年龄2岁5个月)在常规组治疗基础上予左卡尼汀治疗.选择同期在郑州大学附属儿童医院体检的健康儿童40例作为健康对照组.比较健康对照组和HFMD患儿血清中S100、NSE、可溶性凋亡相关因子(sFas)和可溶性凋亡相关因子配体(sFasL)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平,2组HFMD患儿治疗前后脑脊液和血清中上述指标水平,发热持续时间、治疗第3天白细胞计数、神经系统症状缓解时间、病情进展时间、危重型转化率等疗效相关指标,sFas、sFasL、MDA、SOD与S100和NSE相关性分析.结果 1.HFMD组患儿血清中S100[(0.38±0.16) μg/L比(0.06±0.23) μg/L]、NSE[(43.70±8.80) μg/L比(10.10±3.60) μg/L]、sFas[(6.61±1.86) μg/L比(3.88±1.22)μg/L]、sFasL[(101.40±20.7) μg/L比(54.4±13.3) μg/L]、MDA[(11.98±2.54) nmol/L比(4.08±1.45) nmol/L]水平较健康对照组显著增高,差异均有统计学意义(t=-12.245、-22.895、-8.273、-12.803、-17.960,均P＜0.05);SOD[(57.10±10.40)kU/L比(70.3±14.4) kU/L]水平明显降低,差异有统计学意义(--5.457,P＜0.05).2.2组HFMD患儿随治疗时间延长脑脊液S100、NSE和血清中S100、NSE、sFas、sFasL、MDA整体下降,SOD水平升高;治疗后第3天和第7天左卡尼汀组患儿脑脊液S100(t3 =3.491,t7=14.434)、NSE(t3=2.920,t7=23.490)、血清S100 (t3=5.277,t7 =3.614)、NSE(t3 =4.652,t7=10.525)、sFas(t3 =6.399,t7 =7.514)、sFasL(t3=11.155,t7=8.804)、MDA(t3=6.348,t7=7.499)均显著低于常规组(均P＜0.05),SOD(t3=3.162,t7=-3.529)显著高于常规组(均P＜0.05).3.左卡尼汀组患儿神经系统症状缓解时间显著短于常规组[(1.23±0.65)d比(1.84±0.47)d],治疗第3天白细胞计数[(9.14±2.93)×109/L比(7.12±2.58)×109/L]、病情进展时间[(29.74±7.85)h比(17.36±8.73)h]均显著优于常规组(t=-6.178、4.204、8.567,均P＜0.05).左卡尼汀组和常规组患儿危重型转化率分别为7.58％和18.18％,危重型转化率比较差异无统计学意义(x2=2.316,P＞0.05).4.HFMD患儿S100与sFas、sFasL、MDA呈正相关(r=0.373、0.735、0.334,均P＜0.05),NSE与sFas、sFasL均呈正相关(r=0.479、0.601,均P＜0.05),SOD与S100和NSE均呈负相关(r=-0.425、-0.460,均P＜0.05).结论 左卡尼汀治疗儿童EV71感染重症手足口病疗效较好,可有效保护脑神经,其机制可能与清除氧自由基和阻断神经细胞凋亡有关.

abstractsObjective To observe the neuro-protective effect of Levocarnitine on severe hand,foot and mouth disease (HFMD) after enterovirus 71 (EV71) infection,to preliminarily explore the possible mechanism preliminarily.Methods One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Chihlren's Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases,including 32 males and 34 females,median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levocarnitine group (66 cases,including 36 males and 30 females,median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females,median age of 2 years and 6 months) who were examined at the Children's Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100,NSE,soluble apoptosis-related factors (sFas),soluble apoptosis-related factor l igands (sFasL),malondialdehyde (MDA),superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum,efficacy-related indicators such as duration of fever,white blood cell count on the 3rd day of treatment,time to remission of nervous system symptoms,time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas,sFasL,MDA,SOD and S100,NSEwas performed Results (1) The levels of S100 [(0.38:±:0.16) μg/Lvs.(0.06:±:0.23) μg/L],NSE [(43.70±8.80) μg/Lvs.10.10±3.60) μg/L],sFas [(6.61 ±1.86) μg/Lvs.(3.88±1.22) μg/L],sFasL [(101.40±20.7) μg/Lvs.(54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/Lvs.(4.08±1.45) nmol/L]in serum of HFMD group were significantly higher than those of the healthy control group (t =-12.245,-22.895,-8.273,-12.803,-17.960,all P ＜0.05),while the SOD level [(57.10 ± 10.40) kU/L vs.(70.3 ±14.4) kU/L] was significantly lower (t =5.457,P ＜ 0.05).(2) With the extension of treatment time for HFMD children in the two groups,S100 and NSE in cerebrospinal fluid,S100,NSE,sFas,sFasL and MDA in serum decreased,while SOD level increased.On the 3rd and 7th day after treatment,S100 (t3 =3.491,t7 =14.434),NSE (t3 =2.920,t7 =23.490) in cerebrospinal fluid,S100 (t3 =5.277,t7 =3.614),NSE (t3 =4.652,t7 =10.525),sFas (t3 =6.399,t7 =7.514),sFasL (t3 =11.155,t7 =8.804) and MDA (t3 =6.348,t7 =7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P ＜ O.05),while SOD (t3 =3.162,t7 =-3.529) was significantly higher than that of routine group (P ＜0.05).(3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23 ± 0.65) d vs.(1.84 ± 0.47) d],and WBC on the 3rd day after treatment [(9.14 ± 2.93) × 109/L vs.(7.12 ± 2.58) × 109/L] and the progression time of the disease [(29.74 ± 7.85) h vs.(17.36 ± 8.73) h] were significantly better than the those in the routine group (t =-6.178,4.204,8.567,all P ＜ 0.05).The critical conversion rates of Levocarnitine group and the routine group were 7.58％ and 18.18％,respectively,and the difference in critical conversion rate was not statistically significant (x2 =2.316,P ＞0.05).(4)There was a positive correlation between S100 and sFas,sFasL,MDA in children with HFMD (r =0.373,0.735,0.334,P ＜ 0.05).NSE was positively correlated with sFas and sFasL (r =0.479,0.601,all P ＜0.05),while SOD and S100 were negatively correlated with NSE (r =-0.425,-0.460,all P ＜ 0.05).Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71,which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.