趙香麗，王蕾，田麗

（東明縣婦幼保健院，山東東明274500；*菏澤市立醫(yī)院,山東菏澤274000）

鼠神經(jīng)生長(zhǎng)因子治療小兒急性中毒性腦病療效及對(duì)心肌酶與炎性因子的影響

趙香麗，王蕾＊，田麗＊

（東明縣婦幼保健院，山東東明274500；*菏澤市立醫(yī)院,山東菏澤274000）

目的探討鼠神經(jīng)生長(zhǎng)因子治療小兒急性中毒性腦病的療效及對(duì)心肌酶與炎性因子的影響。方法急性中毒性腦病患兒88例，隨機(jī)分為對(duì)照組30例，治療組58例。對(duì)照組給予相應(yīng)的病因及對(duì)癥治療。治療組在此基礎(chǔ)上，加用鼠神經(jīng)生長(zhǎng)因子15天為一療程。治療1個(gè)月、2個(gè)月、3個(gè)月比較兩組患兒神經(jīng)癥狀、運(yùn)動(dòng)功能障礙等改善及頭顱MRI改變情況。入院后第1天和治療90天后抽空腹靜脈血檢測(cè)CK、CKMB、AST、LDH、HBD、IL-1、IL-6、IL-8、IL-10、TNF-α水平變化。應(yīng)用SPSS20.0軟件，所獲數(shù)據(jù)采用方差分析、t檢驗(yàn)和χ2檢驗(yàn)。結(jié)果治療組58例，神經(jīng)癥狀改善52例，占89.65%；運(yùn)動(dòng)功能改善44例，占75.86%；頭顱MRI改善48例，占82.7%，總有效率為89.65%。對(duì)照組30例，神經(jīng)癥狀改善9例，占30.00%；運(yùn)動(dòng)功能改善15例，占50.00%；頭顱MRI改善10例，占33.33%，總有效率為66.67%。兩組比較，P＜0.01。所有病例未發(fā)現(xiàn)有明顯過(guò)敏反應(yīng)。對(duì)照組治療前后CK水平變化比較，P＜0.05；治療前后CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005。治療組治療前后CK、CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005；兩組治療后CK、CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005。對(duì)照組治療前后血清IL-1、IL-8、TNF-α水平變化比較，P均＜0.0005；對(duì)照組治療前后血清IL-6、IL-10水平變化比較，P均＜0.005。治療組治療前后血清IL-1、IL-6、IL-8、IL-10、TNF-α水平變化比較，P均＜0.0005。兩組治療后血清IL-1、IL-8、IL-10、TNF-α水平變化比較，P均＜0.0005；兩組治療后血清IL-6水平變化比較，P＜0.001。結(jié)論鼠神經(jīng)生長(zhǎng)因子能夠明顯改善急性中毒性腦病患兒的神經(jīng)、運(yùn)動(dòng)功能，具有顯著的治療效果，隨著病情的好轉(zhuǎn)心肌酶及炎性因子也逐漸恢復(fù)正常。

鼠神經(jīng)生長(zhǎng)因子/治療應(yīng)用；小兒急性中毒性腦病/治療；心肌酶；炎性因子

中毒性腦病是嬰幼兒期比較常見(jiàn)的中樞神經(jīng)系統(tǒng)病變，是因毒素進(jìn)入腦內(nèi)、損害腦細(xì)胞所致，故稱(chēng)為中毒性腦病。小兒急性中毒性腦病是重癥感染性或中毒性疾病常見(jiàn)的并發(fā)癥之一，臨床病情兇險(xiǎn)，可導(dǎo)致呼吸衰竭和死亡。容易留有眾多的并發(fā)癥及嚴(yán)重后遺癥。多數(shù)侵犯1～3歲的小兒，病情重，原發(fā)病后幾天或1～2周出現(xiàn)大腦損害癥狀。發(fā)病急驟，突然出現(xiàn)高熱、頭痛、嘔吐、煩躁或嗜睡、肢涼、面色蒼白、尿少、驚厥和昏迷。臨床表現(xiàn)因腦部病變輕重程度不同多種多樣[1]。為提高疾病治愈率，減少后遺癥的發(fā)生，我們自2013年8月—2016年8月間采用鼠神經(jīng)生長(zhǎng)因子治療急性中毒性腦病，取得了滿意療效，現(xiàn)報(bào)道如下。

1 臨床資料

1.1 一般資料中毒性腦病患兒88例，均符合診斷標(biāo)準(zhǔn)［1］。男49例，女39例，年齡6個(gè)月～14歲。平均2.86歲。隨機(jī)分為兩組，對(duì)照組30例，治療組58例。兩組在性別、年齡大小等一般資料比較，P＞0.05,無(wú)顯著性差異，具有可比性。

1.2 治療方法對(duì)照組給予相應(yīng)的病因及對(duì)癥治療。治療組在此基礎(chǔ)上加用鼠神經(jīng)生長(zhǎng)因子2ml注射用水溶解，肌肉注射，每日1次，1個(gè)療程為15天，間隔15天接受第2個(gè)療程治療，共治療3個(gè)療程。均以1個(gè)月、2個(gè)月、3個(gè)月接受治療后的效果進(jìn)行療效評(píng)價(jià)。入院后第1天和治療90天后抽空腹靜脈血檢測(cè)CK、CKMB、AST、LDH、HBD、IL-1、IL-6、IL-8、IL-10、TNF-α水平變化。

1.3 療效判定標(biāo)準(zhǔn)短期療效評(píng)價(jià)標(biāo)準(zhǔn)在治療3個(gè)月后對(duì)兩組患兒的生命體征（體溫、呼吸、心率、血壓）、神經(jīng)癥狀、運(yùn)動(dòng)功能、頭顱MRI改善情況等指標(biāo)復(fù)查。治愈：相關(guān)神經(jīng)、運(yùn)動(dòng)功能障礙癥狀基本消失、頭顱MRI正常，無(wú)并發(fā)癥及后遺癥。有效：相關(guān)神經(jīng)、運(yùn)動(dòng)功能障礙癥狀、頭顱MRI較治療前顯著改善，但在3個(gè)月內(nèi)出現(xiàn)嚴(yán)重并發(fā)癥和后遺癥等。無(wú)效：無(wú)癥狀改善且病情、頭顱MRI加重或醫(yī)治無(wú)效死亡。

1.4 統(tǒng)計(jì)學(xué)處理應(yīng)用SPSS20.0軟件，所獲數(shù)據(jù)采用方差分析、t檢驗(yàn)和χ2檢驗(yàn)。

2 結(jié)果

2.1 兩組治療后神經(jīng)癥狀、運(yùn)動(dòng)功能、頭顱MRI恢復(fù)情況治療組58例，神經(jīng)癥狀改善52例，占89.65%；運(yùn)動(dòng)功能改善44例，占75.86%；頭顱MRI改善48例，占82.7%。治療組治愈38例，占65.52%；好轉(zhuǎn)14例，占24.14%；總有效率為89.65%。對(duì)照組30例，神經(jīng)癥狀改善9例，占30.00%；運(yùn)動(dòng)功能改善15例，占50.00%；頭顱MRI改善10例，占33.33%。對(duì)照組治愈8例，占26.67%；好轉(zhuǎn)12例，占40.00%；總有效率為66.67%。兩組比較，χ2=7.0242，P＜0.01。所有病例未發(fā)現(xiàn)有明顯過(guò)敏反應(yīng)。有3例患者在治療期間用藥后出現(xiàn)局部疼痛伴硬結(jié)，給予局部熱敷結(jié)合土豆片外敷后均好轉(zhuǎn)。

2.2 兩組治療前后心肌酶變化比較見(jiàn)表1。

2.3 兩組治療前后血清IL-1、IL-6、IL-8、IL-10、TNF-α比較見(jiàn)表2。腦水腫的發(fā)生，減輕腦水腫的

表1 兩組治療前后心肌酶變化比較（x-±s）

表2 兩組治療前后血清IL-1、IL-6、IL-8、IL-10、TNF-α比較（x-±s）

3 討論

急性中毒性腦病是各種感染、中毒性疾病危重的并發(fā)癥，常見(jiàn)于敗血癥、肺炎、中毒性痢疾、傷寒、腦膿腫等急性感染性疾病的早期或極期，或是毒氣、飲食不潔、農(nóng)藥、生物毒素、超量口服藥物等，導(dǎo)致神經(jīng)系統(tǒng)受到損害[2]。感染及其毒素增加腦部血管通透性,導(dǎo)致神經(jīng)細(xì)胞腫脹,引起急性彌漫性腦水腫[3],毒素亦可使腦血管痙攣,引起腦組織缺氧和缺血產(chǎn)生中樞神經(jīng)系統(tǒng)癥狀[4]。小兒急性中毒性腦病發(fā)病突然，危害較大，多無(wú)特效治療藥物，緊急救治以對(duì)癥治療為主，積極控制驚厥，解除腦水腫，積極恢復(fù)大腦神經(jīng)細(xì)胞功能是治療成功的關(guān)鍵!應(yīng)用神經(jīng)生長(zhǎng)因子治療缺氧缺血性腦損傷大鼠，可明顯延緩大鼠程度。減少腦細(xì)胞凋亡而使腦損傷減輕，起到保護(hù)腦組織的作用[5]。同時(shí)可促進(jìn)運(yùn)動(dòng)神經(jīng)元的存活和復(fù)蘇發(fā)生細(xì)胞凋亡和軸突變性的運(yùn)動(dòng)神經(jīng)元[6]。還可調(diào)節(jié)膠質(zhì)細(xì)胞反應(yīng)，促進(jìn)星形膠質(zhì)細(xì)胞增殖[7]。神經(jīng)生長(zhǎng)因子不僅可以營(yíng)養(yǎng)正常成熟神經(jīng)細(xì)胞，更重要的是對(duì)損傷的神經(jīng)細(xì)胞起保護(hù)和修復(fù)作用。

通過(guò)3個(gè)月的治療與觀察，治療組總有效率為89.65%，對(duì)照組總有效率為66.67%。兩組比較，P＜0.01，治療組明顯優(yōu)于對(duì)照組。所有病例未發(fā)現(xiàn)有明顯過(guò)敏反應(yīng)。對(duì)照組治療前后CK水平變化比較，P＜0.05；對(duì)照組治療前后CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005。治療組治療前后CK、CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005。兩組治療后CK、CKMB、AST、LDH、HBD水平變化比較，P均＜0.0005。通過(guò)治療后兩組心肌酶均有明顯好轉(zhuǎn)，治療更顯著，基本恢復(fù)正常[5]。急性腦病時(shí)，啟動(dòng)了白細(xì)胞趨化因子系統(tǒng)，通過(guò)治療3個(gè)月后。對(duì)照組治療前后血清IL-1、IL-8、TNF-α水平變化比較，P均＜0.0005；對(duì)照組治療前后血清IL-6、IL-10水平變化比較，P均＜0.005。治療組治療前后血清IL-1、IL-6、IL-8、IL-10、TNF-α水平變化比較，P均＜0.0005。兩組治療后血清IL-1、IL-8、IL-10、TNF-α水平變化比較，P均＜0.0005；兩組治療后血清IL-6水平變化比較，P＜0.001。說(shuō)明治療組效果較顯著，恢復(fù)快、后遺癥少[8]。

［1］吳滬生,葉其芬.神經(jīng)系統(tǒng)感染性疾病.見(jiàn):胡亞美,江載芳,諸福棠.實(shí)用兒科學(xué)（下冊(cè)）[M].7版,北京:人民衛(wèi)生出版社,2003: 1864-1865.

［2］王美團(tuán),劉曉亮.新生兒缺氧缺血性腦病血清細(xì)胞因子變化及臨床意義[J].湖南師范大學(xué)學(xué)報(bào)（醫(yī)學(xué)版）,2013,10（2）:67-70.

［3］李淑君,唐義麗,馮自威.小兒重癥肺炎并中毒性腦病的臨床分析[J].中國(guó)實(shí)用神經(jīng)疾病雜志,2010,13（1）:97.

[4]趙春玲,李薔華.中西醫(yī)結(jié)合治療小兒急性中毒性腦病12例[J].中國(guó)中醫(yī)急癥,2001,（6）:363.

[5]劉濤.嬰幼兒輪狀病毒腸炎血清心肌酶譜變化統(tǒng)計(jì)分析[J].中國(guó)衛(wèi)生統(tǒng)計(jì),2010,27（3）:333.

.[6]嚴(yán)超英,周文莉,徐乃軍.外周應(yīng)用神經(jīng)生長(zhǎng)因子對(duì)新生大鼠缺氧缺血腦損傷的保護(hù)作用[J].中國(guó)新生兒科雜志2007,22(2):93-94. [7]徐發(fā)林,朱長(zhǎng)連,程永秀,等.窒息新生兒血清及腦脊液細(xì)胞因子變化及其與雨后的關(guān)系[J].實(shí)用兒科臨床雜志,2005,20（8）:732-735.

[8]尹曉娟,劉冬云,羅分.鼠源性神經(jīng)生長(zhǎng)因子對(duì)缺氧缺血性腦損傷大鼠海馬膠質(zhì)纖維酸性蛋白表達(dá)的影響[J].中國(guó)小兒急救醫(yī)學(xué), 2009,16（4）352-354

The Eeffect of Rat Nerve Growth Factor on the Treatment of Acute Toxic Encephalopathy in Children and Its Effect on Myocardial Enzymes and Inflammatory Factors

Zhao Xiangli,Wang lei*,Tian Li*
(Maternal and Child Care Service Hospital in Dongming County,Dongming 274500,Shandong;*Heze Municipal Hospital,Heze 274000,Shandong)

ObjectiveTo investigate the effect of rat nerve growth factor on the treatment of acute toxic encepha?lopathy in children and its effect on myocardial enzymes and inflammatory factors.Methods 88 cases of acute toxic en?cephalopathy were randomly divided into control group.The treatment group was 58 cases.The control group was given corresponding treatment for the cause and symptomatic treatment.On this basis,the treatment group was treated with 15 days of rat nerve growth factor.In January,February and march,the improvement of neurological symptoms,motor dys?function,and other improvement of the head MRI were compared in the two groups.After the first day of admission and the treatment of the patients after 90 days,the patients with ventral venous blood were found to have the horizontal chang?es of CK,CKMB,AST,LDH,HBD,il-1,il-6,il-8,il-10,and TNF-alpha.Using SPSS20.0 software,the data obtained were variance analysis,t test and χ2test.Results58 cases of neurological symptoms in the treatment group were improved by 52 cases,accounting for 89.65%.Motor function improved 44 cases,accounting for 75.86%.Skull MRI im?proved 48 cases,accounting for 82.7%.The total effective rate of treatment was 89.65%.In the control group,there were 30 cases and 9 cases of neurological improvement,accounting for 30.00%.Motor function improved 15 cases,accounting for 50.00%.Skull MRI was improved in 10 cases,33.33%.Total effective rate of control group was 66.67%.Comparison of the two groups,P＜0.01.No significant allergic reactions were found in all cases.Comparison of CK level changes be?fore and after treatment in the control group,P＜0.05.Compared with the changes of CKMB,AST,LDH and HBD in the control group,P was＜0.0005.The changes of CK,CKMB,AST,LDH and HBD were compared before and after treat?ment group,P was＜0.0005.After treatment,the changes of CK,CKMB,AST,LDH and HBD were compared with P＜0.0005.Comparison of serum il-1,il-8 and TNF-alpha in the control group was compared with P＜0.0005.Comparison of serum il-6 and il-10 levels in the control group was compared with P＜0.005.The serum il-1,il-6,il-8,il-10 and TNF-alpha were compared in the treatment group before and after treatment,with P＜0.0005.The serum il-1,il-8,il-10 and TNF-alpha were compared in the two groups after treatment,with P＜0.0005.Comparison of serum il-6 levels af?ter treatment was compared with P＜0.001.Conclusionthe rat nerve growth factor can significantly improve the nerve and motor function of children with acute toxic encephalopathy,and have remarkable therapeutic effect.The myocardial enzyme and inflammatory factor gradually returned to normal as the disease improved.

Rat nerve growth factor/therapeutic use；Acute toxic encephalopathy/therapy；Myocardial enzyme；Inflammatory cytokines

R-365

A

1008-4118（2017）03-0063-04

2017-05-25

10.3969/j.issn.1008-4118.2017.03.020