李鳴,李強(qiáng),張媚,張細(xì)六,胡琴,龐艷

(武漢市第五醫(yī)院1.神經(jīng)內(nèi)科;2.檢驗(yàn)科,武漢 430050)

丹紅注射液對(duì)急性腦梗死患者血清S100B蛋白和神經(jīng)元特異性烯醇化酶的影響

李鳴1,李強(qiáng)1,張媚1,張細(xì)六1,胡琴1,龐艷2

(武漢市第五醫(yī)院1.神經(jīng)內(nèi)科;2.檢驗(yàn)科,武漢 430050)

目的 探討丹紅注射液對(duì)急性腦梗死(ACI)患者血清S100B蛋白和神經(jīng)元特異性烯醇化酶(NSE)水平的影響及臨床療效。方法ACI患者80例,隨機(jī)分為治療組及對(duì)照組,每組40例。對(duì)照組根據(jù)《中國(guó)急性缺血性腦卒中診治指南》給予常規(guī)治療,治療組另加丹紅注射液,治療14 d。在起病1,3,5,10 d時(shí)測(cè)定血清S100B蛋白和NSE水平的變化,每例患者在起病1,21 d時(shí)分別行美國(guó)國(guó)立衛(wèi)生研究院卒中量表(NIHSS)評(píng)分。結(jié)果治療組在3,5 d時(shí)S100B及NSE水平明顯低于對(duì)照組(P＜0.01),21 d時(shí)兩組NIHSS評(píng)分較治療前均明顯減少,治療組評(píng)分低于對(duì)照組(P＜0.05)。治療組及對(duì)照組血清S100B蛋白峰值濃度與腦梗死后1 d時(shí)NIHSS評(píng)分均呈正相關(guān)(分別r=0.761,r=0.792,均P＜0.01),兩組血清NSE水平與腦梗死后1 d時(shí)NIHSS評(píng)分均呈正相關(guān)(分別r=0.734,r=0.756,均P＜0.01)。結(jié)論丹紅注射液能降低急性腦梗死患者血清S100B及NES水平,促進(jìn)神經(jīng)功能恢復(fù)。

丹紅注射液;腦梗死,急性;S100B蛋白;神經(jīng)元特異性烯醇化酶

急性腦梗死(acute cerebral infarction,ACI)是目前危害人類健康的主要疾病之一,近年來(lái)動(dòng)物實(shí)驗(yàn)和臨床研究發(fā)現(xiàn),在ACI時(shí),血清S100B蛋白水平變化程度可反映神經(jīng)膠質(zhì)細(xì)胞損傷的嚴(yán)重程度[1],血清神經(jīng)元特異性烯醇化酶(neuron-specific enolase,NSE)是觀察腦內(nèi)神經(jīng)元損傷和壞死的客觀特異性指標(biāo)[2-3],ACI后血清S100B及NSE升高水平與患者病情的嚴(yán)重程度及預(yù)后密切相關(guān)[4-5]。筆者通過(guò)觀察血清S100B及NSE濃度的變化,以及丹紅注射液的干預(yù)作用,結(jié)合臨床療效觀察,探討丹紅注射液對(duì)急性腦梗死患者的療效。

1 資料與方法

1.1 臨床資料 選擇發(fā)病時(shí)間在6～24 h的首次發(fā)作,并經(jīng)頭部CT或磁共振(MRI)證實(shí)的急性腦梗死患者80例,患者已超過(guò)溶栓時(shí)間窗,均不適合溶栓治療。排除標(biāo)準(zhǔn):有嚴(yán)重肝、腎功能不全,活動(dòng)性消化道潰瘍者;癡呆、精神異常無(wú)法合作者;惡性腫瘤;血液病,凝血功能異常。隨機(jī)分為治療組及對(duì)照組,每組40例:治療組男31例,女9例,年齡48～76歲;對(duì)照組男32例,女8例,年齡50～74歲。兩組在年齡、性別、危險(xiǎn)因素(糖尿病、高脂血癥、吸煙、高血壓病)、入院時(shí)病情程度[美國(guó)國(guó)立衛(wèi)生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)]等方面均差異無(wú)統(tǒng)計(jì)學(xué)意義。

1.2 治療方法 對(duì)照組給予阿司匹林100～300 mg口服,qd,1周后改為100 mg·d-1,不能耐受阿司匹林者給予氯吡格雷片75 mg,qd,并按照《中國(guó)急性腦梗死診治指南》2010年版[6]的要求,給予調(diào)脂、控制血壓、控制血糖、神經(jīng)保護(hù)等治療,如有嚴(yán)重腦水腫及顱內(nèi)壓增高,可使用脫水等治療,治療組在對(duì)照組治療基礎(chǔ)上,加丹紅注射液(濟(jì)南步長(zhǎng)制藥有限公司生產(chǎn),批準(zhǔn)文號(hào):國(guó)藥準(zhǔn)字Z20026866)30 mL加入到0.9%氯化鈉注射液250 mL中,qd,靜脈滴注,療程為14 d。

1.3 觀察指標(biāo) 在起病1,3,5,10 d測(cè)定血清S100B蛋白和NSE水平,S100B及NSE試劑均購(gòu)自德國(guó)羅氏診斷有限公司,應(yīng)用電化學(xué)發(fā)光法,使用羅氏cobas e 601全自動(dòng)電化學(xué)發(fā)光免疫分析儀測(cè)定S100B及NSE值。每個(gè)患者在發(fā)病1及21 d時(shí)分別行NIHSS評(píng)分。

2 結(jié)果

2.1 兩組各時(shí)間點(diǎn)血清S100B蛋白和NSE水平變化比較 結(jié)果顯示,血清S100B蛋白和NSE水平在腦梗死起病1 d時(shí)已經(jīng)開(kāi)始明顯升高,兩組差異無(wú)統(tǒng)計(jì)學(xué)意義,起病約3 d升高達(dá)高峰,起病5 d明顯下降,起病10 d基本恢復(fù)到正常水平。與對(duì)照組比較,在起病3及5 d,治療組此兩項(xiàng)指標(biāo)下降更為明顯,差異有統(tǒng)計(jì)學(xué)意義(P＜0.01)。見(jiàn)表1。

2.2 兩組治療前后NIHSS評(píng)分比較 對(duì)照組和治療組治療前NIHSS評(píng)分分別(13.53±4.23),(12.91± 4.52)分;起病21 d后分別為(7.57±3.18),(5.83± 2.88)分?？梢?jiàn)兩組起病21 d的NIHSS評(píng)分均較治療前明顯好轉(zhuǎn),治療組優(yōu)于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。

表1 兩組患者血清S100B蛋白和NSE水平比較Tab.1 Comparison of the serum level of S100B p rotein and NSE between two groups of patients μg·L-1,±s

表1 兩組患者血清S100B蛋白和NSE水平比較Tab.1 Comparison of the serum level of S100B p rotein and NSE between two groups of patients μg·L-1,±s

與對(duì)照組同時(shí)間點(diǎn)比較,*1P＜0.01Compared with control group at the same time point,*1P＜0.01

S100B NSE對(duì)照組組別與時(shí)間例數(shù)40 1 d 0.81±0.28 26.95±5.95 3 d 1.23±0.35 37.40±8.15 5 d 0.79±0.22 24.17±5.43 10 d 0.21±0.12 16.24±3.60治療組40 1 d 0.78±0.25 25.56±4.80 3 d 1.01±0.33*128.91±7.69*15 d 0.50±0.21*118.91±4.00*110 d 0.19±0.14 14.87±3.32

2.3 兩組血清S100B蛋白和NSE濃度峰值與起病1 d NIHSS評(píng)分相關(guān)性分析 治療組及對(duì)照組血清S100B蛋白峰值濃度與起病1 d NIHSS評(píng)分均呈正相關(guān)(分別r=0.761,r=0.792,均P＜0.01),治療組及對(duì)照組血清NSE峰值濃度與起病1 d NIHSS評(píng)分均呈正相關(guān)(分別r=0.734,r=0.756,均P＜0.01)。

3 討論

S100B蛋白主要存在于中樞神經(jīng)系統(tǒng)的星形膠質(zhì)細(xì)胞和少突膠質(zhì)細(xì)胞,是一種鈣依耐性調(diào)控蛋白,通過(guò)信號(hào)傳導(dǎo),調(diào)控細(xì)胞內(nèi)外蛋白或細(xì)胞的活性,可以修復(fù)、活化受損的神經(jīng)元和膠質(zhì)細(xì)胞,正常濃度的S100B對(duì)神經(jīng)細(xì)胞起到營(yíng)養(yǎng)作用,但高濃度的S100B有神經(jīng)毒素作用,可引起神經(jīng)細(xì)胞的凋亡[7-8]。在急性腦梗死時(shí),細(xì)胞內(nèi)的S100B蛋白可釋放到腦脊液中,經(jīng)受損的血-腦屏障進(jìn)入血液。血清S100B濃度在起病24～120 h內(nèi)升高至峰值[1],作為中樞神經(jīng)系統(tǒng)疾病的生化標(biāo)志物,其水平變化程度與神經(jīng)膠質(zhì)細(xì)胞損傷的嚴(yán)重程度以及臨床預(yù)后直接相關(guān)[9-10]。NSE特異性地存在于神經(jīng)元和神經(jīng)內(nèi)分泌細(xì)胞中,是維持神經(jīng)元細(xì)胞膜興奮性的必需成分。急性腦梗死時(shí),神經(jīng)元出現(xiàn)損傷或壞死,NSE可迅速?gòu)募?xì)胞內(nèi)釋放并進(jìn)入細(xì)胞間隙,通過(guò)腦脊液及血-腦脊液屏障進(jìn)入外周血,血清NSE水平在發(fā)病早期即開(kāi)始增高,1～4 d達(dá)高峰,然后隨著病情好轉(zhuǎn)逐漸下降[5],與患者短期預(yù)后正相關(guān)[11]。聯(lián)合檢測(cè)NSE和S100B蛋白能較全面評(píng)價(jià)神經(jīng)元及神經(jīng)膠質(zhì)細(xì)胞損傷嚴(yán)重程度,作為急性腦梗死患者病情判斷和預(yù)后評(píng)價(jià)的血清學(xué)標(biāo)志物。

兩組患者血清S100B蛋白及NSE在起病后明顯升高,約3 d達(dá)到峰值,且峰值濃度與起病1 d時(shí)患者NIHSS評(píng)分正相關(guān),提示此兩項(xiàng)指標(biāo)可以作為反應(yīng)腦梗死嚴(yán)重程度的標(biāo)志。在腦梗死起病3,5 d時(shí),治療組血清S100B蛋白及NSE濃度明顯低于對(duì)照組,提示治療組神經(jīng)元及神經(jīng)膠質(zhì)細(xì)胞損傷程度小于對(duì)照組。起病21 d時(shí),兩組NIHSS評(píng)分均有下降,但治療組較對(duì)照組下降更明顯。臨床證實(shí)丹紅注射劑治療急性缺血性腦卒中可以減小神經(jīng)功能損傷程度,有益于神經(jīng)功能恢復(fù)。

丹紅注射液是由中藥丹參和紅花提取精制而成,其主要有效成分包括丹參酮、丹參酚酸、紅花黃色素等。其治療急性腦梗死可能機(jī)制包括:①抑制血小板粘附、聚集,激活和釋放血栓素A2,激活血管內(nèi)皮細(xì)胞釋放前列環(huán)素,抑制血栓形成[12]。②促進(jìn)側(cè)支循環(huán)的建立與開(kāi)放,恢復(fù)梗死周邊缺血半暗區(qū)腦細(xì)胞的功能,減輕神經(jīng)功能損傷,對(duì)局灶腦缺血有明顯的治療作用[13]。③使腦梗死區(qū)域星形膠質(zhì)細(xì)胞增殖,加強(qiáng)突觸重建和功能修復(fù),促進(jìn)運(yùn)動(dòng)功能恢復(fù)[14]。④改善血液流變學(xué)、降低纖維蛋白原含量[15]。⑤降低腦梗死患者血漿內(nèi)皮素-1水平,抑制炎癥因子的表達(dá),改善血管內(nèi)皮的功能,起到血管保護(hù)作用,并且減輕腦水腫,從而改善患者神經(jīng)功能缺損評(píng)分及預(yù)后[16-17]。丹紅注射液可能通過(guò)以上機(jī)制達(dá)到減輕神經(jīng)元及神經(jīng)膠質(zhì)細(xì)胞損傷,促進(jìn)神經(jīng)功能恢復(fù)的作用。

急性缺血性腦卒中時(shí),影響血清S100B及NSE濃度的因素除腦梗死范圍外,還與腦梗死部位、應(yīng)激反應(yīng)的強(qiáng)弱、并發(fā)感染等因素有關(guān),且不同病情程度患者S100B及NSE濃度變化時(shí)間可能存在差異。本研究未做亞組統(tǒng)計(jì)比較,在以后的研究中,將擴(kuò)大樣本量,進(jìn)行亞組比較,增加檢測(cè)樣本時(shí)間點(diǎn),進(jìn)一步探討丹紅注射液治療急性腦梗死的療效及可能的機(jī)制。

[1] NASH D L,BELLOLIOM F,STEAD LG.S100 as amarker of acute brain ischemia:a systematic review[J]. Neurocritical Care,2008,8(2):301-307.

[2] WUNDERLICH M T,LINSH,SKALE JM,et al.Neuronspecific enolase and tau protein as neurobiochemical markers of neuronal damage are related to early clinical course and long-term outcome in acute ischemic stroke[J]. Clin Neurol Neurosurg,2006,108(6):558-563.

[3] NOAMAN A,ELSHAFEY R,SHAHAWY A,et al.MR spec-troscopy,S100B protein and NSE analysis as early predictors of hypoxic ischemic encephalopathy[J].Egypt J Radiol Nuc Med,2013,44(2):309-320.

[4] SERGIO G,ALINA G,OTMAN F,et al.Short-term prog-nostic value of serum neuron specific enolase and S100B in acute stroke patients[J].Clin Biochem,2012,45(7): 1302-1307.

[5] LAMERS K J,VOS P,VERBEEK M M,et al.Protein S-100B,neuron-specific enolase(NSE),myelin basic protein (MBP)and glial fibrillary acidic protein(GFAP)in cerebrospinal fluid(CSF)and blood of neurological patients [J].Brain Res Bull,2003,61(4):261-264.

[6] 中華醫(yī)學(xué)會(huì)神經(jīng)病學(xué)分會(huì)腦血管病學(xué)組急性腦梗死診治指南撰寫組.中國(guó)急性腦梗死診治指南2010[J].中華神經(jīng)科雜志,2010,43(2):146-153.

[7] MORIT,TAN J,ARENDASH GW,etal.Overexpression of human S100B exacerbates brain damage and perinfarct gliosis after permanent focal ischemia[J].Stroke,2008,39 (10):2114-2121.

[8] DONATO R,SORCIG,RIUZZI F,et al.S100B's double life:Intracellular regulator and extracellular signal[J]. Biochim Biophys Acta,2009,1793(11):1008-1022.

[9] RODRIGUEZ-RODRIGUEZ A,JUAN JOSE E G,ANTONIO L J,etal.Role of S100B protein in urine and serum as an early predictor ofmortality after severe traumatic brain injury in adults[J].Clinica Chimica Acta,2012,414(9): 228-233.

[10] YUAN X S,BIAN X.S100B protein and its clinical effect on craniocerebral injury[J].Chinese J Traumatol,2008,11 (1):54-57.

[11] RUNDGRENA M,KARLSSON T,NIELSEN N,et al.Neuronspecific enolase and S100B as predictors of outcome after cardiac arrest and induced hypothermia[J]. Resuscitation,2009,80(7):784-789.

[12] 王淑君,王萬(wàn)鐵,熊建華,等.紅花注射液對(duì)腦缺血-再灌注損傷家兔血漿TXA2/PGI2水平的影響[J].中國(guó)現(xiàn)代應(yīng)用藥學(xué),2003,20(2):100-102.

[13] 鄧芬,胡長(zhǎng)林,謝運(yùn)蘭.丹紅注射液治療大鼠急性腦梗死的實(shí)驗(yàn)研究[J].中西醫(yī)結(jié)合心腦血管病雜志,2007,5 (5):421-423.

[14] 譚來(lái)勛,段申漢,曾慶杏,等.丹紅注射劑對(duì)大鼠腦梗死灶周突觸和星形膠質(zhì)細(xì)胞的影響[J].中國(guó)醫(yī)師雜志, 2007,9(8):1009-1012.

[15] 于華,李萍,高見(jiàn)朋.丹紅注射液對(duì)急性腦梗死患者血液流變學(xué)的影響[J].中國(guó)醫(yī)學(xué)創(chuàng)新,2010,7(20):45-46.

[16] 冶學(xué)蘭,趙秀麗.丹紅注射液對(duì)急性腦梗死患者內(nèi)皮素的影響[J].中西醫(yī)結(jié)合心腦血管病雜志,2009,7(1): 116-117.

[17] 胡安義,劉莉.丹紅注射液對(duì)不穩(wěn)定型心絞痛患者血管內(nèi)皮功能及炎癥因子的影響[J].醫(yī)藥導(dǎo)報(bào),2011,30 (3):319-321.

DOI 10.3870/yydb.2014.12.014

Effect of Danhong Injection on Levels of Serum S100B Protein and Neuron-specific Enolase in Patientswith Acute Cerebral Infarction

LIMing1,LIQiang1,ZHANG Mei1,ZHANG Xi-liu1,HU Qin1,PANG Yan2
(1.Departmetn of Neurology;2. Clinical Laboratory,the Fifth Hospital ofWuhan,Wuhan 430050,China)

Objective To observe influence ofdanhonginjection on levels of serum S100B protein and neuron-specific enolase(NSE)in patients with acute cerebral infarction(ACI),and to explore its clinical effect.MethodsEighty cases of ACIwere random ly divided into treatment group and control group with 40 cases in each group.Both groups were given routine treatment according to the clinical guideline.Treatment group receiveddanhonginjection once a day for14 days.Levels of serum S100B protein and NSE were detected 1,3,5 and 10 days after ACI.The patients in the two groups were evaluated by NIHSS 1 and 21 day(s)after ACI.ResultsCompared with control group,levels of serum S100B protein and NSE were significantly lower in treatment group than in control group 3 and 5 days after ACI(allP＜0.01).NIHSS scores were significantly decreased 21 days after ACI in both groups,and NIHSS scores were lower in treatment group than in control group(P＜0.05).Peak concentration of S100B protein in treatment group and control group was positively correlated with NIHSS scores(r=0.761 andr=0.792,respectively,bothP＜0.01).ConclusionDanhonginjection can decrease serum S100B and NSE levels,and improve the neurological function in ACIpatients.

Danhonginjection;Cerebral infarction,acute;S100B protein;Neuron-specific enolase

R286;R743.3

A

1004-0781(2014)12-1596-04

2013-09-02

2014-02-12

李鳴(1975-),男,湖北襄陽(yáng)人,副主任醫(yī)師,碩士,主要從事腦血管病研究。電話:(0)18602702599,E-mail: 18602702599@163.com。