安宫牛黄丸联合神经节苷脂治疗儿童病毒性脑炎的临床研究
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摘要
目的观察安宫牛黄丸联合单唾液酸四己糖神经节苷脂钠注射液治疗儿童病毒性脑炎的临床疗效。方法选取2016年12月—2017年12月新乡市中心医院收治的128例病毒性脑炎患儿作为研究对象,采用随机数表法将所有患儿随机分为对照组和治疗组,每组各64例。对照组静脉滴注单唾液酸四己糖神经节苷脂钠注射液,20 mg加入10%的葡萄糖溶液100 mL中,1次/d。治疗组在对照组的基础上口服或鼻饲安宫牛黄丸,3岁以下患儿每次1/4丸,4～6岁每次1/2丸,7～13岁每次1丸,生理盐水15～20mL研成匀浆,每日1～2次。两组患儿均连续治疗2周。观察两组患者的临床疗效,同时比较两组治疗前后的临床症状、体征改善情况、神经功能指标、炎症因子水平和脑脊液检查结果。结果治疗后,对照组和治疗组的总有效率分别为76.57%、96.88%,两组比较差异具有统计学意义(P<0.05)。治疗后,治疗组呕吐消失时间、意识清醒时间、头痛消失时间、锥体束征消失时间均显著短于对照组,两组比较差异具有统计学意义(P<0.05)。治疗后,两组血清S100β蛋白、神经元特异性烯醇化酶(NSE)、神经生长因子(NGF)、髓磷脂碱性蛋白(MBP)水平均显著降低,同组治疗前后比较差异具有统计学意义(P<0.05);治疗后治疗组S100β、NSE、NGF、MBP水平显著低于对照组,两组比较差异具有统计学意义(P<0.05)。治疗后,两组血清白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平均显著降低,同组治疗前后比较差异具有统计学意义(P<0.05);治疗后治疗组血清IL-1、TNF-α、CRP水平显著低于对照组,两组比较差异具有统计学意义(P<0.05)。治疗后,两组总细胞数、单核细胞数、蛋白含量均显著降低,同组治疗前后比较差异具有统计学意义(P<0.05);治疗后治疗组总细胞数、蛋白含量显著低于对照组,两组比较差异具有统计学意义(P<0.05)。结论安宫牛黄丸联合单唾液酸四己糖神经节苷脂钠注射液可显著提高病毒性脑炎临床疗效,改善患儿的临床症状和神经功能,减轻炎症反应,具有一定的临床推广应用价值。
Objective To observe the clinical effect of Angong Niuhuang Pills combined with Monosialotetrahexosylganglioside Sodium Injection in treatment of viral encephalitis in children. Methods Children(128 cases) with viral encephalitis in Xinxiang Central Hospital from December 2016 to December 2017 were randomly divided into control and treatment groups, and each group had 64 cases. Children in the control group were iv administered with Monosialotetrahexosylganglioside Sodium Injection, 20 mg added into 10% glucose solution 100 mL, once daily. Children in the treatment group were po or nasal feeding administered with Angong Niuhuang Pills on the basis of the control group, 1/4 pill per time for children under 3 years old, 1/2 pill per time for children aged 4 — 6 years old, and 1 pill per time for children aged 7 — 13 years old. The pills were ground into homogenate with 15 — 20 mL normal saline, 1 — 2 times daily. Children in two groups were treated for 2 weeks. After treatment, clinical efficacy was evaluated, and the clinical symptoms and signs recovery time, neurological function indexes, inflammatory factors level, and the cerebrospinal fluid examination results in two groups before and after treatment were compared. Results After treatment, the clinical efficacies in the control and treatment groups were 76.57% and 96.88%, respectively, and there were differences between two groups(P < 0.05). After treatment, the time of vomiting disappearance, consciousness awakening, headache disappearance, and pyramidal tract sign disappearance in the treatment group were significantly shorter than those in the control group, and there were differences between two groups(P < 0.05). After treatment, the levels of S100β, NSE, NGF, and MBP in two groups were significantly decreased,and the difference was statistically significant in the same group(P < 0.05). After treatment, the levels of S100β, NSE, NGF, and MBP in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P <0.05). After treatment, the levels of IL-1, TNF-α, and CRP in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). After treatment, the levels of IL-1, TNF-α, and CRP in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P < 0.05). After treatment, the total cell number, monocyte number, and protein content in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). After treatment, the total cell number and protein content in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P < 0.05). Conclusion Angong Niuhuang Pills combined with Monosialotetrahexosylganglioside Sodium Injection can significantly improve the clinical efficacy of viral encephalitis, improve clinical symptoms and neurological function of children, and reduce inflammatory response, which has a certain clinical application value.
Objective To observe the clinical effect of Angong Niuhuang Pills combined with Monosialotetrahexosylganglioside Sodium Injection in treatment of viral encephalitis in children. Methods Children(128 cases) with viral encephalitis in Xinxiang Central Hospital from December 2016 to December 2017 were randomly divided into control and treatment groups, and each group had 64 cases. Children in the control group were iv administered with Monosialotetrahexosylganglioside Sodium Injection, 20 mg added into 10% glucose solution 100 mL, once daily. Children in the treatment group were po or nasal feeding administered with Angong Niuhuang Pills on the basis of the control group, 1/4 pill per time for children under 3 years old, 1/2 pill per time for children aged 4 — 6 years old, and 1 pill per time for children aged 7 — 13 years old. The pills were ground into homogenate with 15 — 20 mL normal saline, 1 — 2 times daily. Children in two groups were treated for 2 weeks. After treatment, clinical efficacy was evaluated, and the clinical symptoms and signs recovery time, neurological function indexes, inflammatory factors level, and the cerebrospinal fluid examination results in two groups before and after treatment were compared. Results After treatment, the clinical efficacies in the control and treatment groups were 76.57% and 96.88%, respectively, and there were differences between two groups(P < 0.05). After treatment, the time of vomiting disappearance, consciousness awakening, headache disappearance, and pyramidal tract sign disappearance in the treatment group were significantly shorter than those in the control group, and there were differences between two groups(P < 0.05). After treatment, the levels of S100β, NSE, NGF, and MBP in two groups were significantly decreased,and the difference was statistically significant in the same group(P < 0.05). After treatment, the levels of S100β, NSE, NGF, and MBP in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P <0.05). After treatment, the levels of IL-1, TNF-α, and CRP in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). After treatment, the levels of IL-1, TNF-α, and CRP in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P < 0.05). After treatment, the total cell number, monocyte number, and protein content in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). After treatment, the total cell number and protein content in the treatment group were significantly lower than those in the control group, with significant difference between two groups(P < 0.05). Conclusion Angong Niuhuang Pills combined with Monosialotetrahexosylganglioside Sodium Injection can significantly improve the clinical efficacy of viral encephalitis, improve clinical symptoms and neurological function of children, and reduce inflammatory response, which has a certain clinical application value.
引文
[1]胡文静,杨理明,廖红梅,等.小儿重症病毒性脑炎临床特点、预后及其相关因素分析[J].中国感染控制杂志,2018,17(3):241-246.
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[3]Palmano K,Rowan A,Guillermo R,et al.The role of gangliosides in neurodevelopment[J].Nutrients,2015,7(5):3891-3913.
[4]邓玲玲,田莉,王洪才.安宫牛黄丸及其演化方剂的临床研究进展[J].中国实验方剂学杂志,2010,16(12):215-219.
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[7]于盼辉,王佶,李静洁,等.2015年~2016年石家庄地区儿童病毒性脑炎病原学研究[J].病毒学报,2017,33(2):180-185.
[8]Dubey D,Pittock S J,Kelly C R,et al.Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis[J].Ann Neurol,2018,83(1):166-177.
[9]黄亮,俞丹,罗蓉,等.儿童病毒性脑炎急性期临床病理特征对继发癫痫的影响[J].四川大学学报:医学版,2017,48(2):257-262.
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[11]李红星,苑国富,金耀东,等.神经干细胞移植联用神经节苷脂对脑损伤大鼠神经学功能恢复的影响[J].中国组织工程研究与临床康复,2011,15(40):7505-7510.
[12]王珂,杨会娟,马俊,等.神经节苷脂-1与康复训练对缺血缺氧性脑损伤大鼠神经功能的影响[J].中国康复理论与实践,2014,20(1):34-36.
[13]García J D,Córdoba M,Cuba A,et al.Gangliosides minimize motor disabilities and histopathological changes in cortical lesioned and transplanted rats[J].Arch Med Res,1996,27(4):465-471.
[14]张红爱,王玲,冷钦,等.缺氧缺血新生鼠海马磷酸化环磷酸腺苷反应元件结合蛋白的变化及神经节苷酯对其影响[J].中华实用儿科临床杂志,2004,19(4):283-284.
[15]董世芬,楼黎明,张硕峰,等.安宫牛黄丸(含天然麝香或人工麝香)对实验性脑缺血的保护作用[J].世界科学技术:中医药现代化,2013,15(1):85-90.
[16]李玉静.神经元特异性烯醇化酶对病毒性脑炎患者脑损伤的评估价值[D].石家庄:河北医科大学,2012.
[17]陈锋,张芙蓉,孙继民,等.亚低温对重症病毒性脑炎患儿血清及脑脊液NSE、S100β蛋白表达的影响[J].华中科技大学学报:医学版,2017,46(3):291-294.
[18]Libich D S,Ahmed M A,Zhong L,et al.Fuzzy complexes of myelin basic protein:NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system[J].Biochem Cell Biol,2010,88(2):143-155.
[19]朱凤莲,石太新,白海涛,等.病毒性脑炎患儿脑脊液髓鞘碱性蛋白的测定及临床意义[J].中华实用儿科临床杂志,2001,16(3):165-166.
[20]Skoldenberg B,Aurelius E,Hjalmarsson A,et al.Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults[J].J Neurol,2006,253(2):163-170.
[21]Li Y C,Xi C H,An Y F,et al.Perioperative inflammatory response and protein S-100βconcentrations-relationship with post-operative cognitive dysfunction in elderly patients[J].Acta Anaesthesiol Scand,2012,56(5):595-600.
[22]Labroo P,Goodwin I,Davis B,et al.Abstract 132:Effect of NGF delivering conduit on peripheral nerve regeneration[J].Plast Reconstr Surg Glob Open,2017,5(4 Suppl):97-98.
[23]Athar P,Hasbun R,Nolan M S,et al.Long-term neuromuscular outcomes of west nile virus infection:Aclinical and electromyographic evaluation of patients with a history of infection[J].Muscle Nerve,2018,57(1):77-82.
[24]高世超,曹敬荣,王培昌.中枢神经系统病毒性感染的实验室诊断研究进展[J].中华实验和临床感染病杂志:电子版,2017,11(3):218-221.
[25]Ironson G,Lucette A,Hylton E,et al.The relationship between religious and psychospiritual measures and an inflammation marker(CRP)in older adults experiencing life event stress[J].J Relig Health,2018,57(4):1554-1566.
[26]Guttmann A,Pillinger M H,Krasnokutsky S.Autoimmune tracheal cartilage inflammation responsive to anti-TNF-αtherapy[J].Bull Hosp Jt Dis,2018,76(2):139-142.
[27]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.
[28]Christensen J E,Simonsen S,Fenger C,et al.Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokinechemokine cascade[J].J Immunol,2009,182(2):1079-1087.
[2]Zambito Marsala S,Pistacchi M,Gioulis M,et al.Neurological complications of tick borne encephalitis:the experience of 89 patients studied and literature review[J].Neurol Sci,2014,35(1):15-21.
[3]Palmano K,Rowan A,Guillermo R,et al.The role of gangliosides in neurodevelopment[J].Nutrients,2015,7(5):3891-3913.
[4]邓玲玲,田莉,王洪才.安宫牛黄丸及其演化方剂的临床研究进展[J].中国实验方剂学杂志,2010,16(12):215-219.
[5]贾建平.神经病学[M].第6版.北京:人民卫生出版社,2008:233-234.
[6]孙明,王蔚文.临床疾病诊断及疗效判定标准[M].北京:科学技术文献出版社,2010:34-35.
[7]于盼辉,王佶,李静洁,等.2015年~2016年石家庄地区儿童病毒性脑炎病原学研究[J].病毒学报,2017,33(2):180-185.
[8]Dubey D,Pittock S J,Kelly C R,et al.Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis[J].Ann Neurol,2018,83(1):166-177.
[9]黄亮,俞丹,罗蓉,等.儿童病毒性脑炎急性期临床病理特征对继发癫痫的影响[J].四川大学学报:医学版,2017,48(2):257-262.
[10]Irani,David N,Prow,et al.Acute Viral Encephalitis:Role of the Immune System in Viral Clearance from the CNSand in the Generation of Pathology[M].New York:Cambridge University Press,2010:125-136.
[11]李红星,苑国富,金耀东,等.神经干细胞移植联用神经节苷脂对脑损伤大鼠神经学功能恢复的影响[J].中国组织工程研究与临床康复,2011,15(40):7505-7510.
[12]王珂,杨会娟,马俊,等.神经节苷脂-1与康复训练对缺血缺氧性脑损伤大鼠神经功能的影响[J].中国康复理论与实践,2014,20(1):34-36.
[13]García J D,Córdoba M,Cuba A,et al.Gangliosides minimize motor disabilities and histopathological changes in cortical lesioned and transplanted rats[J].Arch Med Res,1996,27(4):465-471.
[14]张红爱,王玲,冷钦,等.缺氧缺血新生鼠海马磷酸化环磷酸腺苷反应元件结合蛋白的变化及神经节苷酯对其影响[J].中华实用儿科临床杂志,2004,19(4):283-284.
[15]董世芬,楼黎明,张硕峰,等.安宫牛黄丸(含天然麝香或人工麝香)对实验性脑缺血的保护作用[J].世界科学技术:中医药现代化,2013,15(1):85-90.
[16]李玉静.神经元特异性烯醇化酶对病毒性脑炎患者脑损伤的评估价值[D].石家庄:河北医科大学,2012.
[17]陈锋,张芙蓉,孙继民,等.亚低温对重症病毒性脑炎患儿血清及脑脊液NSE、S100β蛋白表达的影响[J].华中科技大学学报:医学版,2017,46(3):291-294.
[18]Libich D S,Ahmed M A,Zhong L,et al.Fuzzy complexes of myelin basic protein:NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system[J].Biochem Cell Biol,2010,88(2):143-155.
[19]朱凤莲,石太新,白海涛,等.病毒性脑炎患儿脑脊液髓鞘碱性蛋白的测定及临床意义[J].中华实用儿科临床杂志,2001,16(3):165-166.
[20]Skoldenberg B,Aurelius E,Hjalmarsson A,et al.Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults[J].J Neurol,2006,253(2):163-170.
[21]Li Y C,Xi C H,An Y F,et al.Perioperative inflammatory response and protein S-100βconcentrations-relationship with post-operative cognitive dysfunction in elderly patients[J].Acta Anaesthesiol Scand,2012,56(5):595-600.
[22]Labroo P,Goodwin I,Davis B,et al.Abstract 132:Effect of NGF delivering conduit on peripheral nerve regeneration[J].Plast Reconstr Surg Glob Open,2017,5(4 Suppl):97-98.
[23]Athar P,Hasbun R,Nolan M S,et al.Long-term neuromuscular outcomes of west nile virus infection:Aclinical and electromyographic evaluation of patients with a history of infection[J].Muscle Nerve,2018,57(1):77-82.
[24]高世超,曹敬荣,王培昌.中枢神经系统病毒性感染的实验室诊断研究进展[J].中华实验和临床感染病杂志:电子版,2017,11(3):218-221.
[25]Ironson G,Lucette A,Hylton E,et al.The relationship between religious and psychospiritual measures and an inflammation marker(CRP)in older adults experiencing life event stress[J].J Relig Health,2018,57(4):1554-1566.
[26]Guttmann A,Pillinger M H,Krasnokutsky S.Autoimmune tracheal cartilage inflammation responsive to anti-TNF-αtherapy[J].Bull Hosp Jt Dis,2018,76(2):139-142.
[27]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.
[28]Christensen J E,Simonsen S,Fenger C,et al.Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokinechemokine cascade[J].J Immunol,2009,182(2):1079-1087.