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手足口病(hand, foot and mouth disease,HFMD)多发生于5岁以下儿童,其传播具有季节性和较大范围的流行性,交叉传染率高,病情进展迅速可致死。目前柯萨奇病毒A16(CVA16)和肠道病毒71(EV71)是HFMD主要的病原[1]。EV71感染导致的HFMD相比CVA16更易出现严重并发症,包括脑膜炎、脑炎、脑脊髓炎、神经源性肺水肿、循环障碍、新生儿脓毒症等[2-3],死亡率较高,自2008年以来全国统计的死亡病例为1 490例。HFMD已成为发展中国家重大的公共卫生关切[4]。然而至今没有特效的抗病毒药物,因此,识别HFMD高危患儿并尽力避免神经源性肺水肿(neurogenic pulmonary edema,NPE)等危重情况出现是当下儿科面临的困境。
HFMD典型的临床表现包括发热,咽痛,口腔黏膜、手足部或臀部皮肤红色丘疹样皮疹。NPE和循环衰竭是重症HFMD患儿病情快速进展并恶化的重要临床征象。EV71感染后侵犯脑干引起交感神经兴奋从而导致大量儿茶酚胺释放,主要包括去甲肾上腺素(norepinephrine,NE)、肾上腺素和多巴胺。儿茶酚胺的增多可引起白细胞介素6(interleukin-6)、IL-1、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)等促炎或抗炎细胞因子的激活和释放[2-3]。其中,IL-6是肺部损伤难以逆转可能的关键因素。本研究观察EV71感染HFMD患儿不同临床分期NE、IL-6的浓度变化并分析其与病情进展的相关性,结合临床表现探讨对病情演变的影响。
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各组研究对象性别、年龄、肢体抖动情况差异无统计学意义(P>0.05)。随着HFMD进展,EV71感染患儿的临床症状包括高热持续72 h、精神差、呕吐、易激惹、呼吸困难、心率增快、CRT>2 s、WBC>15×109/L、Glu>8.3 mmol/L出现的比例逐渐增加(P < 0.05~P < 0.01)(见表 1)。
项目 对照组(n=30) EV71感染Ⅱ期(n=30) EV71感染Ⅲ期(n=30) EV71感染Ⅳ期(n=20) χ2 P 性别(男/女) 19/11 19/11 21/9 12/8 0.61 >0.05 年龄/月 30.22±10.54 29.33±11.12 27.62±11.31 23.18±10.22 1.89* >0.05 高热持续72 h 0(0.00) 19(63.33) 20(66.67) 19(95.00) 8.11 < 0.05 精神差 0(0.00) 7(23.33) 14(46.67) 16(80.00) 32.76 < 0.01 呕吐 0(0.00) 3(10.00) 9(30.00) 16(80.00) 65.00 < 0.01 易激惹 0(0.00) 6(20.00) 21(70.00) 16(80.00) 41.19 < 0.01 肢体抖动 0(0.00) 21(70.00) 27(90.00) 20(100.00) 5.38 >0.05 呼吸困难 0(0.00) 3(10.00) 4(13.33) 10(50.00) 40.80 < 0.01 心率增快 0(0.00) 9(30.00) 14(46.67) 18(90.00) 34.36 < 0.01 CRT>2 s 0(0.00) 1(3.33) 16(53.33) 13(65.00) 53.62 < 0.01 WBC>15×109/L 0(0.00) 12(40.00) 13(43.33) 17(85.00) 22.61 < 0.01 Glu>8.3 mmol/L 0(0.00) 15(50.00) 17(56.67) 15(75.00) 7.90 < 0.05 *示F值 表 1 各组研究对象一般情况比较[n;百分率(%)]
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NE和IL-6在EV71感染HFMD患儿Ⅱ、Ⅲ、Ⅳ期的血浓度水平均明显高于对照组(P < 0.01),且随着HFMD进展逐渐升高(P < 0.01)(见表 2)。
分组 n NE IL-6 对照组 30 0.47±0.39 47.84±26.53 EV71感染Ⅱ期 30 5.69±3.46** 90.83±33.91** EV71感染Ⅲ期 30 10.84±4.61**△△ 148.94±78.24**△△ EV71感染Ⅳ期 20 18.94±4.81**△△## 202.69±57.14**△△## F — 112.87 41.10 P — < 0.01 < 0.01 MS组内 — 13.28 2 767.13 q检验:与对照组比较**P < 0.01;与EV71感染Ⅱ期比较△△P < 0.01;与EV71感染Ⅲ期比较##P < 0.01 表 2 各组研究对象NE和IL-6的变化情况(x±s;pg/mL)
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Pearson相关分析显示,EV71感染HFMD患儿IL-6与NE的血浓度变化水平呈正相关关系(r=0.413,P<0.05)。
EV71感染手足口病患儿去甲肾上腺素、IL-6变化趋势及作用
Change and effect of norepinephrine and interleukin-6 in HFMD children infected by EV71
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摘要:
目的观察肠道病毒71(EV71)感染手足口病患儿Ⅱ、Ⅲ、Ⅳ期去甲肾上腺素(NE)、白细胞介素6(IL-6)的变化趋势,探讨其表达与病情进展的相关性。 方法比较健康儿童与EV-71感染手足口病患儿Ⅱ、Ⅲ、Ⅳ期的临床表现及实验室检查差异,检测不同阶段血液中NE、IL-6的浓度并分析二者与病情演进相关性。 结果随着HFMD进展,EV71感染患儿的临床症状包括高热持续72 h、精神差、呕吐、易激惹、呼吸困难、心率增快、毛细血管再充盈时间>2 s、白细胞计数>15×109/L、葡萄糖>8.3 mmol/L出现的比例逐渐增加(P < 0.05~P < 0.01)。NE和IL-6在EV71感染HFMD患儿Ⅱ、Ⅲ、Ⅳ期的血浓度水平均明显高于对照组(P < 0.01),且随着EV-71感染分期递增其水平逐渐升高(P < 0.01)。Pearson相关分析显示,EV71感染HFMD患儿IL-6与NE的血浓度变化水平呈正相关关系(r=0.413,P < 0.05)。 结论手足口病患儿NE、IL-6水平随EV-71感染分期递增并行升高可能是EV-71感染后病情进展的重要因素,提示临床医生可能通过分析NE、IL-6水平评估患儿病情。 Abstract:ObjectiveTo observe the levels of norepinephrine(NE) and interleukin-6(IL-6) during the stage Ⅱ, Ⅲ and Ⅳ hand foot mouth disease(HFMD) children infected by enterovirus 71(EV71), and investigate the correlation of levels of NE and IL-6 with EV71 infection. MethodsThe differences of the clinical presentation and laboratory examination among stage Ⅱ, Ⅲ and Ⅳ HFMD children infected by EV71 and healthy children were compared.The levels of NE and IL-6 in different period were detected, and the correlation of levels of NE and IL-6 with disease progression were analyzed. ResultsWith the progression of HFMD, the proportions of EV71 infection children with duration 72 h of high fever, poor spirit, vomiting, irritability, dysphasia, rapid heart rate, capillary refill time >2 s, white blood cell >15×109/L and glucose >8.3 mmol/L gradually increased(P < 0.05 to P < 0.01).The levels of NE and IL-6 in EV71 infection stage Ⅱ, Ⅲ and Ⅳ children were significantly higher than those in healthy children, and which gradually increased with the increasing of EV71 infection staging(P < 0.01).The results of Pearson correlation analysis showed that the level of IL-6 was positively correlated with NE level in EV71 infection children(P < 0.01). ConclusionsThe levels of NE and IL-6 in HFMD increasing with the progression of EV71 infection staging may be an important factor for the disease progression after EV71 infection, which hints that clinicians can evaluate the children's condition by analyzing the levels of NE and IL-6. -
Key words:
- hand, foot and mouth disease /
- enterovirus 71 /
- norepinephrine /
- interleukin-6
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表 1 各组研究对象一般情况比较[n;百分率(%)]
项目 对照组(n=30) EV71感染Ⅱ期(n=30) EV71感染Ⅲ期(n=30) EV71感染Ⅳ期(n=20) χ2 P 性别(男/女) 19/11 19/11 21/9 12/8 0.61 >0.05 年龄/月 30.22±10.54 29.33±11.12 27.62±11.31 23.18±10.22 1.89* >0.05 高热持续72 h 0(0.00) 19(63.33) 20(66.67) 19(95.00) 8.11 < 0.05 精神差 0(0.00) 7(23.33) 14(46.67) 16(80.00) 32.76 < 0.01 呕吐 0(0.00) 3(10.00) 9(30.00) 16(80.00) 65.00 < 0.01 易激惹 0(0.00) 6(20.00) 21(70.00) 16(80.00) 41.19 < 0.01 肢体抖动 0(0.00) 21(70.00) 27(90.00) 20(100.00) 5.38 >0.05 呼吸困难 0(0.00) 3(10.00) 4(13.33) 10(50.00) 40.80 < 0.01 心率增快 0(0.00) 9(30.00) 14(46.67) 18(90.00) 34.36 < 0.01 CRT>2 s 0(0.00) 1(3.33) 16(53.33) 13(65.00) 53.62 < 0.01 WBC>15×109/L 0(0.00) 12(40.00) 13(43.33) 17(85.00) 22.61 < 0.01 Glu>8.3 mmol/L 0(0.00) 15(50.00) 17(56.67) 15(75.00) 7.90 < 0.05 *示F值 表 2 各组研究对象NE和IL-6的变化情况(x±s;pg/mL)
分组 n NE IL-6 对照组 30 0.47±0.39 47.84±26.53 EV71感染Ⅱ期 30 5.69±3.46** 90.83±33.91** EV71感染Ⅲ期 30 10.84±4.61**△△ 148.94±78.24**△△ EV71感染Ⅳ期 20 18.94±4.81**△△## 202.69±57.14**△△## F — 112.87 41.10 P — < 0.01 < 0.01 MS组内 — 13.28 2 767.13 q检验:与对照组比较**P < 0.01;与EV71感染Ⅱ期比较△△P < 0.01;与EV71感染Ⅲ期比较##P < 0.01 -
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