恩再適治療帶狀皰疹后遺神經(jīng)痛療效評(píng)價(jià)及對(duì)BDNF表達(dá)的影響

孔 兵綦佩妍林紅旗

恩再適治療帶狀皰疹后遺神經(jīng)痛療效評(píng)價(jià)及對(duì)BDNF表達(dá)的影響

孔 兵1綦佩妍2林紅旗3

目的: 評(píng)價(jià)牛痘疫苗致炎兔皮提取物(恩再適)治療帶狀皰疹后遺神經(jīng)痛(PHN)的療效及對(duì)腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF)表達(dá)的影響。方法: 50例PHN患者隨機(jī)分為兩組,對(duì)照組給予加巴噴丁、甲鈷胺和對(duì)乙酰氨基酚曲馬多,治療組在此基礎(chǔ)上加用恩再適注射液,療程14天。采用視覺模擬評(píng)分法(VAS)對(duì)患者進(jìn)行疼痛評(píng)分并采用酶聯(lián)免疫吸附法檢測(cè)患者外周血中腦源性神經(jīng)營(yíng)養(yǎng)因子的表達(dá)。結(jié)果: 治療組疼痛評(píng)分較對(duì)照組明顯減少(P＜0.01),治療組外周血中腦源性神經(jīng)營(yíng)養(yǎng)因子表達(dá)較對(duì)照組明顯升高(P＜0.01)。結(jié)論: 恩再適能顯著緩解帶狀皰疹后遺神經(jīng)痛,其作用機(jī)制與BDNF升高密切相關(guān)。

帶狀皰疹后遺神經(jīng)痛； 腦源性神經(jīng)營(yíng)養(yǎng)因子

恩再適即牛痘疫苗致炎兔皮提取物注射液,具有鎮(zhèn)痛、調(diào)節(jié)神經(jīng)、抗變態(tài)反應(yīng)、營(yíng)養(yǎng)神經(jīng)等藥理學(xué)作用,常應(yīng)用于帶狀皰疹后遺神經(jīng)痛(PHN)的治療。本實(shí)驗(yàn)對(duì)恩再適治療PHN患者的療效及對(duì)外周血腦源性神經(jīng)營(yíng)養(yǎng)因子(brain－deriv neurotrophic factor,BDNF)表達(dá)的影響進(jìn)行研究。

1 病例與方法

1.1 病例 50例患者均符合PHN診斷標(biāo)準(zhǔn),視覺模擬評(píng)分法(VAS)疼痛評(píng)分≥4分。排除標(biāo)準(zhǔn):患有高血壓、糖尿病、肝腎功能不全、神經(jīng)精神系統(tǒng)疾病,中途退出或改變治療方案及不能按時(shí)復(fù)診者等。

1.2 治療方法 患者隨機(jī)分為兩組,每組25例,兩組性別、年齡、VAS評(píng)分,無明顯統(tǒng)計(jì)學(xué)差異。對(duì)照組給予加巴噴丁膠囊300 mg日3次,甲鈷胺注射液500 μg肌注日1次,必要時(shí)給予對(duì)乙酰氨基酚曲馬多1片治療。實(shí)驗(yàn)組在對(duì)照組治療基礎(chǔ)上加用恩再適3.6單位加入10 m L生理鹽水中靜脈注射,日1次。兩組均于14天后觀察療效。

1.3 標(biāo)本采集 治療開始前及治療結(jié)束后分別抽取肘前靜脈空腹血10 m L,置于含有促凝凝膠的血清分離管中,室溫下靜置1 h,3000 r/min離心10 min,取血清放置于－80℃冰箱中備用。標(biāo)本測(cè)定前避免反復(fù)凍融。采用酶聯(lián)免疫吸附法測(cè)定血清中BDNF濃度, 96孔板型人BDNF定量檢測(cè)試劑盒購(gòu)于德國(guó)R＆D Systerms GmbH,試劑盒檢測(cè)范圍在0.375～12 g/L,操作步驟嚴(yán)格按照試劑盒說明書進(jìn)行操作。

1.4 疼痛評(píng)分 采用10 cm視覺模擬評(píng)分法(VAS)。參考評(píng)分標(biāo)準(zhǔn):0～1無疼痛癥狀；2～4,輕度疼痛,不影響正常活動(dòng)；5～7,中度疼痛,發(fā)作時(shí)影響正?；顒?dòng)；8～10,重度疼痛,發(fā)作時(shí)必須臥床。

1.5 統(tǒng)計(jì)學(xué)方法 所有數(shù)據(jù)錄入計(jì)算機(jī),用SPSS 16.0統(tǒng)計(jì)軟件包進(jìn)行統(tǒng)計(jì),兩變量間比較采用t檢驗(yàn),兩變量間相關(guān)性采用直線相關(guān)性分析。

2 結(jié)果

2.1 兩組疼痛評(píng)分 對(duì)照組和治療組用藥前的疼痛嚴(yán)重程度VAS評(píng)分分別為7.01±1.25、7.02±1.59。兩組治療結(jié)束后VAS評(píng)分均減少,用藥前后VAS比較均有統(tǒng)計(jì)學(xué)差異(P＜0.01)。治療組的VAS評(píng)分(3.02±1.98)明顯低于對(duì)照組(4.95±2.04),兩組間比較差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。

2.2 兩組BDNF表達(dá)的差異 治療前,兩組外周血BDNF濃度比較無明顯差異(P＞0.05)；治療結(jié)束后,兩組外周血中BDNF濃度均上升,但治療組患者外周血中BDNF濃度上升更明顯,具有統(tǒng)計(jì)學(xué)差異(P＜0.05),見表1。

表1 對(duì)照組與治療組患者BDNF的表達(dá)

3 討論

PHN老年患者多見,疼痛頑固而劇烈,常持續(xù)數(shù)月甚至數(shù)年,治療困難。1多賽平、阿米替林等三環(huán)類抗抑郁藥常引起尿潴留、體位性低血壓、心臟傳導(dǎo)阻滯等不良反應(yīng),限制了這些藥物的應(yīng)用。2因此,尋找治療PHN的藥物成為近年來藥物研究的熱點(diǎn)之一。

恩再適是將牛痘疫苗接種到家兔皮膚后所提取的非蛋白性生理活性物質(zhì),主要影響神經(jīng)－免疫－內(nèi)分泌系統(tǒng)的功能,能夠消除慢性疼痛,改善冷感、麻木等感覺異常,并具有調(diào)整植物神經(jīng)功能、調(diào)節(jié)免疫、抗變態(tài)反應(yīng)、細(xì)胞修復(fù)等功能。3恩再適可恢復(fù)神經(jīng)突觸的傳導(dǎo)功能,激活Na＋－K＋泵活性,保護(hù)缺氧狀態(tài)下神經(jīng)元,促進(jìn)神經(jīng)軸突的形成,改善病損神經(jīng)傳導(dǎo)速度,促進(jìn)雪旺細(xì)胞的增殖,4,5通過對(duì)改善末梢血液循環(huán)的作用,增加受損神經(jīng)的血供,促進(jìn)神經(jīng)修復(fù)。其次,恩再適在中樞通過調(diào)節(jié)5－羥色胺能系統(tǒng)及去甲腎上腺素能系統(tǒng)的功能,激活疼痛下行性抑制系統(tǒng),使疼痛感減輕；在外周通過抑制激肽酶活性而減少緩激肽的釋放,緩解化學(xué)性刺激,減輕局部軟組織及神經(jīng)根的水腫,達(dá)到鎮(zhèn)痛的效果,且鎮(zhèn)痛作用不受納洛酮的拮抗也不影響前列腺素的合成。6恩再適通過對(duì)感覺神經(jīng)元散發(fā)活動(dòng)方式異常修補(bǔ)調(diào)節(jié),進(jìn)而修復(fù)受損的神經(jīng)系統(tǒng),改善神經(jīng)過敏狀態(tài),緩解神經(jīng)源性疼痛及伴發(fā)的冷感、麻木等癥狀,7從而達(dá)到鎮(zhèn)痛作用。

BDNF是20世紀(jì)80年代發(fā)現(xiàn)的神經(jīng)營(yíng)養(yǎng)因子家族中的重要成員,可以促進(jìn)多種神經(jīng)元的再生,對(duì)損傷神經(jīng)元具有修復(fù)和保護(hù)作用。8－11BDNF高度集中分布于神經(jīng)系統(tǒng)內(nèi),具有很強(qiáng)的刺激、促進(jìn)神經(jīng)細(xì)胞生長(zhǎng)分化,維持神經(jīng)細(xì)胞正常功能,促進(jìn)損傷神經(jīng)細(xì)胞修復(fù)的功能。12本研究發(fā)現(xiàn),恩再適治療PHN的過程中,外周血中BDNF的濃度明顯上升,且患者的疼痛評(píng)分與BDNF濃度呈明顯負(fù)相關(guān)。由此推測(cè),恩再適的鎮(zhèn)痛作用,可能與BDNF參與了PHN外周神經(jīng)元的修復(fù)過程有關(guān)。

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(收稿:2012－06－19 修回:2012－10－29)

Efficacy and mechanism of analgecine in the treatm ent of postherpetic neuralgia

KONG Bing,QIPei-yan,LIN Hong-qi.Departmen of Anaesthesiology,Maternal and Child Health Hospital of Shandong Province,Jinan,250014

Objective:Toassess theefficacy and determine the possiblemechanism ofanalgecine(extracts from rabbit skin inflamed by vaccine virus for injection)in the treatment of post－h(huán)erpetic neuralgia(PHN).Methods:Fifty patients with PHN were randomly divided into control group(25 cases)and experimental group(25 cases).In addition to the therapy of gabapentin,mecobalamine and acetaminophen tramadol in control group,analgecine was given to the patients in the experimental group.After 14－days treatment,the therapeutic effectswere evaluated using visual analogue scale(VAS),and the levels of brain－derived neurotrophic factor weremeasured by enzyme linked immunosorbentassay.Results:Compared to the control group, the score of VASwas decreased(P＜0.01)and the level of brain－derived neurotrophic factorwere up－regulated(P＜0.01).Conclusion:Analgecine can reduce the pain of patients with PHN,in which themechanism of the therapeutic effect is closely related to the increase in the level of brain－derived neurotrophic factor.

postherpetic neuralgia；brain－derived neurotrophic factor

1山東省立醫(yī)院婦產(chǎn)醫(yī)院麻醉科,濟(jì)南,250014

2廣東省開平出入境檢疫檢疫局,開平,529300

3濟(jì)空司令部門診,濟(jì)南,250002