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Lp-PLA2表達(dá)差異程度是否可作為腦卒中患者頸動(dòng)脈內(nèi)膜剝脫術(shù)圍手術(shù)期風(fēng)險(xiǎn)的標(biāo)志物評(píng)估

2016-12-09 05:32:00劉曉佳伍健明張協(xié)軍張秋生黃賢鍵
關(guān)鍵詞:頸動(dòng)脈標(biāo)志物斑塊

劉曉佳 伍健明 張 猛 何 毅 張協(xié)軍 張秋生 黃賢鍵

廣東深圳市第二人民醫(yī)院神經(jīng)外科 深圳 518035

Liu Xiaojia,Wu Jianming,Zhang Meng,He Yi,Zhang Xiejun,Zhang Qiusheng,Huang Xianjian

Departmentof Neurosurgery,Shenzhen Second People’s Hospital,Shenzhen 518035,China

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Lp-PLA2表達(dá)差異程度是否可作為腦卒中患者頸動(dòng)脈內(nèi)膜剝脫術(shù)圍手術(shù)期風(fēng)險(xiǎn)的標(biāo)志物評(píng)估

劉曉佳 伍健明△張 猛 何 毅 張協(xié)軍 張秋生 黃賢鍵

廣東深圳市第二人民醫(yī)院神經(jīng)外科 深圳 518035

目的 分析腦卒中患者頸動(dòng)脈內(nèi)膜剝脫術(shù)(CEA)前后血漿Lp-PLA2水平變化,并評(píng)估Lp-PLA2表達(dá)差異程度與圍手術(shù)期并發(fā)癥風(fēng)險(xiǎn)的關(guān)系。方法 選取CEA治療的腦卒中患者44例,檢測(cè)術(shù)前1周和術(shù)后4周Lp-PLA2蛋白的表達(dá)水平,并進(jìn)行2 a隨訪,統(tǒng)計(jì)圍手術(shù)期并發(fā)癥和腦卒中、血管再狹窄等復(fù)發(fā)情況。結(jié)果 對(duì)缺血性腦卒中的相關(guān)危險(xiǎn)因素進(jìn)行Logistic回歸分析,結(jié)果顯示,以缺血性腦卒中是否發(fā)病為應(yīng)變量,相關(guān)危險(xiǎn)因素,如年齡、性別、吸煙史、高血壓、糖尿病、Lp-PLA2為自變量,得到多元回歸方程:缺血性腦卒中=-2.361+0.796吸煙+0.005 Lp-PLA2。由此得出,Lp-PLA2是缺血性腦卒中的危險(xiǎn)因素(P<0.05)。術(shù)前1周和術(shù)后4周Lp-PLA2蛋白表達(dá)水平顯示,其中表達(dá)差異大31例,表達(dá)差異小13例,并進(jìn)行2 a隨訪。最終發(fā)現(xiàn),表達(dá)差異程度大患者出現(xiàn)腦卒中(P<0.05)和再狹窄(P<0.05)的幾率明顯降低。結(jié)論 Lp-PLA2是缺血性腦卒中的獨(dú)立預(yù)測(cè)因子,且Lp-PLA2表達(dá)水平差異可作為腦卒中患者開展CEA圍手術(shù)期風(fēng)險(xiǎn)預(yù)測(cè)標(biāo)志物。

頸動(dòng)脈內(nèi)膜剝脫術(shù);Lp-PLA2;腦梗死

LiuXiaojia,WuJianming,ZhangMeng,HeYi,ZhangXiejun,ZhangQiusheng,HuangXianjian

DepartmentofNeurosurgery,ShenzhenSecondPeople’sHospital,Shenzhen518035,China

頸動(dòng)脈內(nèi)膜切除術(shù)(CEA)[1-3]和近年來發(fā)展的頸動(dòng)脈支架成形術(shù)(CAS)[4-7]是目前治療的頸動(dòng)脈狹窄的標(biāo)準(zhǔn)手術(shù)。CEA可明顯降低有缺血癥狀且頸動(dòng)脈狹窄程度超過50%患者腦卒中的發(fā)生率。本研究利用卒中篩查的人群優(yōu)勢(shì)以及已熟練開展的CEA手術(shù),結(jié)合血清學(xué)檢測(cè)Lp-PLA2水平及完善的臨床資料收集(術(shù)前和圍手術(shù)期等),進(jìn)而評(píng)估手術(shù)前后Lp-PLA2表達(dá)水平差異程度是否可作為圍手術(shù)期和遠(yuǎn)期復(fù)發(fā)風(fēng)險(xiǎn)評(píng)估的標(biāo)志物。

1 對(duì)象與方法

1.1 病例選擇 研究共納入44例腦卒中患者,病理診斷符合1995年全國(guó)第4屆腦血管疾病學(xué)術(shù)會(huì)議修訂腦梗死診斷標(biāo)準(zhǔn)。所有患者均經(jīng)神經(jīng)系統(tǒng)及MRI等檢查確認(rèn)。除外椎基底動(dòng)脈系統(tǒng)的腦梗死、動(dòng)脈炎、先天發(fā)育異常、糖尿病性、血液成分及血液流變學(xué)所致的腦梗死以及合并冠心病和外周血管病等患者。男23例,女21例;年齡(59.21±8.72)歲;高血壓38例(86.36%),糖尿病11例(25.00%),吸煙史19例(43.18%);Lp-PLA2(27.6±8.52)mmol/L。

1.2 超聲復(fù)查 先作橫向探測(cè),將B超探頭置于頸根部并向頭側(cè)方向移動(dòng):(1)需要測(cè)量血管的內(nèi)徑;(2)識(shí)別膨大部位、頸內(nèi)和頸外動(dòng)脈所在具體位置;(3)監(jiān)測(cè)CCA、ICA和ECA管壁四周所處部位;接著,取頸前側(cè)位再作縱向探測(cè),從頸根部沿著頸總動(dòng)脈血管的長(zhǎng)軸作縱向掃查并越過膨大的部分,顯示頸內(nèi)和頸外動(dòng)脈的長(zhǎng)軸:(1)測(cè)量?jī)?nèi)膜中層的厚度;(2)測(cè)量斑塊長(zhǎng)度和厚度,并觀察其表面和內(nèi)部的特性;(3)用CDFI顯示血管內(nèi)血流的方向、血管充盈情況和狹窄及阻塞的部位;(4)行脈沖多普勒檢查,觀察血流流速曲線,并行參數(shù)測(cè)定。

1.3 血漿Lp-PLA2水平的測(cè)定 于術(shù)前1周和術(shù)后4周空腹采血4 mL,作抗凝處理,標(biāo)本采集后25 min內(nèi)于2~8 ℃情況下1 000×g離心15 min,分離上血清液,置于Ep管內(nèi),統(tǒng)一編號(hào)并保存于-80 ℃條件下。利用免疫增強(qiáng)比濁法測(cè)定血漿中Lp-PLA2含量,具體操作流程按試劑盒說明書進(jìn)行。全部標(biāo)本均一次性成批檢測(cè),以減小批間差和測(cè)量誤差等。并進(jìn)行隨訪,統(tǒng)計(jì)圍手術(shù)期和2 a長(zhǎng)期并發(fā)癥。

1.4 統(tǒng)計(jì)學(xué)方法 采用SPSS 19.0統(tǒng)計(jì)軟件處理數(shù)據(jù)。計(jì)數(shù)資料采用χ2檢驗(yàn),雙側(cè)α=0.05,P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 術(shù)前MRI和術(shù)后切下組織 如圖1所示。

2.2 缺血性腦卒中相關(guān)危險(xiǎn)因素的Logistic回歸分析 對(duì)缺血性腦卒中的相關(guān)危險(xiǎn)因素進(jìn)行Logistic回歸分析,結(jié)果顯示,以缺血性腦卒中是否發(fā)病作為應(yīng)變量,相關(guān)危險(xiǎn)因素,如年齡、性別、吸煙史、高血壓、糖尿病、Lp-PLA2為白變量,得到多元回歸方程:缺血性腦卒中=-2.361+0.796吸煙+0.005 Lp-PLA2。由此得出,Lp-PLA2是缺血性腦卒中的危險(xiǎn)因素(P<0.05)。見表1。

圖1 A:動(dòng)脈管壁MRI增強(qiáng)掃描顯示左側(cè)頸內(nèi)動(dòng)脈起始部狹窄99%(箭頭所示);B:CEA手術(shù)切除的頸動(dòng)脈斑塊

表1 缺血性腦卒中相關(guān)危險(xiǎn)因素的Logistic回歸分析

2.3 CEA手術(shù)前后Lp-PLA2蛋白表達(dá)水平差異程度與圍手術(shù)期并發(fā)癥的關(guān)系 術(shù)前1周和術(shù)后4周Lp-PLA2蛋白表達(dá)水平,其中表達(dá)差異大31例,表達(dá)差異小13例,隨訪2 a示,其中圍手術(shù)期和長(zhǎng)期并發(fā)癥主要包括血腫、腦卒中、心梗、血栓形成、高灌注綜合征、神經(jīng)損傷、喉頭水腫和再狹窄。表達(dá)差異程度大患者出現(xiàn)腦卒中(P<0.05)和再狹窄(P<0.05)的幾率明顯降低。見表2。

表2 CEA手術(shù)前后Lp-PLA2蛋白表達(dá)水平差異程度與圍手術(shù)期并發(fā)癥的關(guān)系

3 討論

缺血性腦卒中(ischemic strokes,IS)是指因腦部血液循環(huán)障礙,腦實(shí)質(zhì)缺血、缺氧所致的局限性腦組織缺血性壞死或軟化,具有高發(fā)病率、高復(fù)發(fā)率和高致殘率等特征[8-9]。新近研究發(fā)現(xiàn),Lp-PLA2作為磷脂酶A2超家族的成員,是一種由441個(gè)氨基酸組成的分子量為45 kD的蛋白質(zhì),該蛋白參與斑塊破裂以及動(dòng)脈血栓形成等諸多過程,目前已被確認(rèn)為預(yù)測(cè)缺血性腦卒中風(fēng)險(xiǎn)及預(yù)后的敏感標(biāo)志物[10]。

CEA和CAS是目前治療的頸動(dòng)脈狹窄的標(biāo)準(zhǔn)手術(shù)[11-12]。循證醫(yī)學(xué)研究證據(jù)表明,CEA可明顯降低有缺血癥狀(即短暫性腦缺血發(fā)作、卒中)且頸動(dòng)脈狹窄≥50%病人腦卒中的發(fā)生率[13-14]。但對(duì)中重度頸動(dòng)脈狹窄(狹窄≥50%)無癥狀患者而言,是否采取手術(shù)治療目前仍有較大爭(zhēng)議[15]。如果此部分患者頸動(dòng)脈斑塊不穩(wěn)定,發(fā)生卒中的風(fēng)險(xiǎn)很高,是手術(shù)干預(yù)的重要指征[16-17]。但現(xiàn)有的檢測(cè)手段包括超聲、CT、MRI、血管造影以及血清學(xué)檢測(cè),難以準(zhǔn)確判斷頸動(dòng)脈斑塊的穩(wěn)定性[18],從而給臨床治療方式的選擇帶來很大困難[19]。因此,迫切需要尋找新的診斷標(biāo)識(shí)評(píng)估頸動(dòng)脈斑塊的穩(wěn)定性。

本研究結(jié)果提示,Lp-PLA2是缺血性腦卒中的危險(xiǎn)因素(P<0.05)。此外,表達(dá)差異程度大患者,出現(xiàn)腦卒中和再狹窄的幾率明顯降低。在徹底切除斑塊后,Lp-PLA2表達(dá)水平可降至最低水平,反之,降低水平不大,復(fù)發(fā)的可能性也就增加。

在一項(xiàng)臨床試驗(yàn)(NASCET)中,研究人員對(duì)500例病人的術(shù)前血管影像學(xué)檢測(cè)結(jié)果與術(shù)后斑塊組織病理分析結(jié)果作了詳細(xì)比較發(fā)現(xiàn),血管影像學(xué)檢出不穩(wěn)定斑塊定的靈敏度只有45.9%,特異性74.0%,總體陽(yáng)性預(yù)測(cè)價(jià)值71%。由此可見,現(xiàn)有手段對(duì)不穩(wěn)定斑塊的檢出率不到50%,假陽(yáng)性率高達(dá)30%。這對(duì)臨床治療方式的選擇(手術(shù)或藥物治療)帶來很大困難,大大降低了頸動(dòng)脈斑塊篩查預(yù)防卒中發(fā)生的效率。

綜上,Lp-PLA2是缺血性腦卒中的獨(dú)立危險(xiǎn)因素,且CEA前后血漿Lp-PLA2變化差異程度可作為腦卒中和血管再狹窄預(yù)測(cè)的潛在標(biāo)志物。

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(收稿2016-06-23)

Evaluation of whether the degree of Lp-PLA2 expression differences can be used as the biomarker for predicting the perioperative risks during CEA for cerebral apoplexy patients

Objective To analyze the Lp-PLA2 expression difference before and after carotid endarterectomy(CEA),and evaluate the association between the degree of expression differences and risk of perioperative complications.Methods These patients who were diagnosed as cerebral apoplexy and adopted CEA surgery,were enrolled in the present cohort.The Lp-PLA2 expression was examined one week before and four weeks after surgery.In addition,the two years follow-up was also conducted,and the complications during perioperative period,cerebral apoplexy and vascular restenosis during the two years follow-up were also recorded.Results A total of 44 patients were enrolled,and the Logistic regression test was performed,by which the cerebral arterial thrombosis was treated as dependent variant and the related risk factors,such as age,sex,smoking status,hypertension,diabetes and Lp-PLA2 were regarded as independent variable,the multiple regression equation was demonstrated as:cerebral arterial thrombosis=-2.361+0.796 smoking status+0.005 Lp-PLA2.Therefore,we can conclude that the Lp-PLA2 was a risk factor for cerebral arterial thrombosis(P<0.05).In addition,we also recorded the Lp-PLA2 expression levels one week before surgery and four weeks after surgery,and identified that a total of 31 cases were of high variability,while 13 cases were of lower variability.After two years’ follow-up,we revealed that these patients with high variability of Lp-PLA2 expression were of significant lower risk to get cerebral apoplexy and restenosis(P<0.05).Conclusion Lp-PLA2 is an independent risk factor for cerebral arterial thrombosis,and the degree of expression differences can be used to predict the risk of perioperative risk during CEA.

Carotid endarterectomy;Lp-PLA2;Cerebral infarction

深圳市科技計(jì)劃項(xiàng)目(JCYJ20140414170821291)

R743.33

A

1673-5110(2016)23-0011-03

△通訊作者:伍建明,主任醫(yī)師,E-mail:wujianmingsz@163.com

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