病毒性脑炎患儿淋巴细胞亚群及免疫因子表达情况与中枢神经损伤的相关性
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摘要
目的探讨病毒性脑炎患儿淋巴细胞亚群及免疫因子表达情况与中枢神经损伤的相关性.方法选取48例病毒性脑炎患儿为研究组,同期的非中枢神经系统感染引起的头痛患儿86例为对照组.应用流式细胞术检测外周血T淋巴细胞亚群,Elisa法检测免疫因子(IL-2,IL-4,IL-6,IL-10,TNF-α,INF-γ,s VCAM-1,P-选择素,L-选择素)和神经损伤分子(NSE,NPT,MBP,S-100)含量.结果研究组CD69+/CD3+CD4+,CD69+/CD3+CD8+表达水平明显低于对照组,差异具有统计学意义(P<0.01); CD25+/CD3+CD4+,HLA-DR+/CD3+CD4+,CD25+/CD3+CD8+,HLA-DR+/CD3+CD8+在两组间比较差异无统计学意义(P>0.05).研究组外周血IL-2表达水平明显低于对照组,IL-6,TNF-α表达水平明显高于对照组,差异具有统计学意义(P<0.05); IL-4,IL-10,INF-γ在两组间表达水平差异无统计学意义(P>0.05).研究组外周血s VCAM-1、P-选择素、L-选择素水平明显高于对照组,差异具有统计学意义(P<0.05).Pearson分析显示:CD69+/CD3+CD4+,CD69+/CD3+CD8+,IL-2与神经损伤分子水平之间呈负相关(P<0.05); IL-6、TNF-α、s VCAM-1、P-选择素、L-选择素与神经损伤分子水平之间呈正相关(P<0.05).结论病毒性脑炎患儿存在免疫功能紊乱,T淋巴细胞亚群活化、炎症因子、s VCAM-1、P-选择素、L-选择素可能参与了病毒性脑炎患儿中枢神经损伤过程.
Objective To investigate the correlation between expression of lymphocyte subsets and immune factors and central nervous system injury in children with viral encephalitis.Method 48 children with viral encephalitis were selected as the study group,while 86 healthy children with non-central nervous system infection during the same period were selected as the control group. T lymphocyte subsets in peripheral blood were detected by flow cytometry,and the contents of immune factors( IL-2,IL-4,IL-6,IL-10,TNF-alpha,INF-gamma,s VCAM-1,Pselectin,L-selectin) and nerve injury molecules( NSE,NPT,MBP,S-100) were detected by Elisa method.Results The expression levels of CD69+/CD3+CD4+,CD69+/CD3+CD8+in the study group were significantly lower than those in the control group( P < 0. 01); there was no significant difference between two groups in CD25+/CD3+CD4+,HLA-DR+/CD3+CD4+,CD25+/CD3+CD8+,HLA-DR+/CD3+CD8+( P>0.05).The expression levels of IL-2,IL-6 and TNF-alpha in peripheral blood of the study group were significantly lower than those of the control group( P < 0. 05),while the expression levels of IL-4,IL-10 and INF-gamma were not significantly different between the two groups( P>0.05).The levels of s VCAM-1,P-selectin and L-selectin in the study group were significantly higher than those in the control group( P <0.05). Pearson analysis showed that CD69+/CD3+CD4+,CD69+/CD3+CD8+,IL-2 were negatively correlated with the molecular level of nerve injury( P<0.05),while IL-6,TNF-α,s VCAM-1,P-selectin and L-selectin were positively correlated with the molecular level of nerve injury( P<0.05).Conclusion Immune dysfunction exists in children with viral encephalitis.T lymphocyte subsets activation,inflammatory factors,s VCAM-1,P-selectin and L-selectin may be involved in the process of central nervous system injury in children with viral encephalitis.
Objective To investigate the correlation between expression of lymphocyte subsets and immune factors and central nervous system injury in children with viral encephalitis.Method 48 children with viral encephalitis were selected as the study group,while 86 healthy children with non-central nervous system infection during the same period were selected as the control group. T lymphocyte subsets in peripheral blood were detected by flow cytometry,and the contents of immune factors( IL-2,IL-4,IL-6,IL-10,TNF-alpha,INF-gamma,s VCAM-1,Pselectin,L-selectin) and nerve injury molecules( NSE,NPT,MBP,S-100) were detected by Elisa method.Results The expression levels of CD69+/CD3+CD4+,CD69+/CD3+CD8+in the study group were significantly lower than those in the control group( P < 0. 01); there was no significant difference between two groups in CD25+/CD3+CD4+,HLA-DR+/CD3+CD4+,CD25+/CD3+CD8+,HLA-DR+/CD3+CD8+( P>0.05).The expression levels of IL-2,IL-6 and TNF-alpha in peripheral blood of the study group were significantly lower than those of the control group( P < 0. 05),while the expression levels of IL-4,IL-10 and INF-gamma were not significantly different between the two groups( P>0.05).The levels of s VCAM-1,P-selectin and L-selectin in the study group were significantly higher than those in the control group( P <0.05). Pearson analysis showed that CD69+/CD3+CD4+,CD69+/CD3+CD8+,IL-2 were negatively correlated with the molecular level of nerve injury( P<0.05),while IL-6,TNF-α,s VCAM-1,P-selectin and L-selectin were positively correlated with the molecular level of nerve injury( P<0.05).Conclusion Immune dysfunction exists in children with viral encephalitis.T lymphocyte subsets activation,inflammatory factors,s VCAM-1,P-selectin and L-selectin may be involved in the process of central nervous system injury in children with viral encephalitis.
引文
[1]王月,杨巧芝,董胜英,等.儿童重症病毒性脑炎预后的影响因素分析[J].山东医药,2015,55(13):93-95.
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[14]邹文菁,占建波,王蕾,等.宜昌市2006-2015年急性脑炎及脑膜炎症候群病原谱分析[J].海南医学,2017,28(5):833-835.
[15]潘可达,方慧,郑默,等.大剂量丙种球蛋白对病毒性脑炎患者脑脊液中血清神经功能指标及相关炎症因子表达水平的影响[J].中华医院感染学杂志,2017,27(9):1929-1932.
[16] Taylor R T,Lubick K J,Robertson S J,et al. TRIM79alpha,an interferon-stimulated gene product,restrictstick-borne encephalitis virus replication by degrading theviral RNA polymerase[J]. Cell Host&Amp; Microbe,2011,10(3):185-196.
[17] Pujhari S K,Prabhakar S,Ratho R,et al. Th1 immuneresponse take over among patients with severe Japaneseencephalitis infection[J]. Journal of Neuroimmunology:Official Bulletin of the Research Committee on Neur-oimmunology of the World Federation of Neurology,2013,263(1/2):133-138.
[18] Thomas Myles Ashhurst,Caryn van Vreden,Luis Munoz-Erazo,et al.Antiviral macrophage responses in flavivirusencephalitis[J]. The Indian Journal of Medical Res-earch,2013,138(5):632-647.
[2]谢晓明.血清及脑脊液MMP-9、TIMP-1水平检测在病毒性脑炎患儿病情评估中的应用价值[J].中国卫生工程学,2018,17(4):591-593.
[3]王燕,黄慧洁,李斌,等.脑脊液中TNF-α、NSE水平对儿童病毒性脑炎影响的Meta分析[J].重庆医学,2017,46(24):3366-3369.
[4]陶维娜,苏红娜,苏红梅,等.儿童重症病毒性脑炎脑电图改变与临床及预后的关系[J].临床荟萃,2013,28(5):549-550.
[5] Adhya D,Dutta K,Kundu K,et al. Histone deacetylaseinhibition by Japanese encephalitis virus in monocyte/macrophages:A novel viral immune evasion strategy[J].Immunobiology:Zeitschrift fur Immunitatsforschung,2013,218(10):1235-1247.
[6]李轲,谢付静,杨亚培,等.单独及联合检测脑脊液中3种标志物对儿童病毒性脑炎与不典型化脓性脑炎的鉴别诊断价值[J].中华实用诊断与治疗杂志,2018,32(4):375-377.
[7]卢蓉,赵力芳,贾鲲鹏,等.小儿病毒性脑炎患儿心肌酶谱、血浆超敏C反应蛋白和胱抑素C水平变化及其临床意义[J].实用心脑肺血管病杂志,2016,24(7):77-79,80.
[8] P illai Sekhar,Tantsis Esther,Prelog Kristina,et al.Confirmed enterovirus encephalitis with associated ster-oidresponsive acute disseminated encephalomyelitis:Anoverlapping infection and inflammation syndrome[J].European Journal of Paediatric Neurology,2015,19(2):266-270.
[9]林创兴,陆学东,林广裕,等.不伴腮腺炎症的腮腺炎病毒性脑膜脑炎患儿临床分析[J].中华实用儿科临床杂志,2017,32(22):1702-1704.
[10]田茂强,李娟,谢新星,等.儿童病毒性脑炎101例病原学及临床研究[J].贵州医药,2017,41(1):73-75.
[11] Valero Nereida,Mosquera Jesus,Alcocer Sirley,et al.Melatonin,minocycline and ascorbic acid reduce oxid-ative stress and viral titers and increase survival rate inexperimental Venezuelan equine encephalitis[J]. Brainresearch,2015,1622:368-376.
[12] P aris Daniel H,Chattopadhyay Suchismita,Jiang Ju,etal.A Nonhuman primate scrub typhus model:protectiveimmune responses induced by pkarp47 dna vaccinationin cynomolgus macaques[J]. The Journal of Immu-nology:Official Journal of the American Association ofImmunologists,2015,194(4):1702-1716.
[13]申辛欣,马学军.病毒性脑炎脑膜炎症候群病原学研究进展[J].中华实验和临床病毒学杂志,2017,31(1):75-78.
[14]邹文菁,占建波,王蕾,等.宜昌市2006-2015年急性脑炎及脑膜炎症候群病原谱分析[J].海南医学,2017,28(5):833-835.
[15]潘可达,方慧,郑默,等.大剂量丙种球蛋白对病毒性脑炎患者脑脊液中血清神经功能指标及相关炎症因子表达水平的影响[J].中华医院感染学杂志,2017,27(9):1929-1932.
[16] Taylor R T,Lubick K J,Robertson S J,et al. TRIM79alpha,an interferon-stimulated gene product,restrictstick-borne encephalitis virus replication by degrading theviral RNA polymerase[J]. Cell Host&Amp; Microbe,2011,10(3):185-196.
[17] Pujhari S K,Prabhakar S,Ratho R,et al. Th1 immuneresponse take over among patients with severe Japaneseencephalitis infection[J]. Journal of Neuroimmunology:Official Bulletin of the Research Committee on Neur-oimmunology of the World Federation of Neurology,2013,263(1/2):133-138.
[18] Thomas Myles Ashhurst,Caryn van Vreden,Luis Munoz-Erazo,et al.Antiviral macrophage responses in flavivirusencephalitis[J]. The Indian Journal of Medical Res-earch,2013,138(5):632-647.