呂建萌，袁 婕，雷 琦，潘雅娟，宋允章，楊 謙

幽門螺桿菌細(xì)胞毒素相關(guān)蛋白A與動(dòng)脈粥樣硬化性腦梗死的關(guān)系

呂建萌，袁 婕，雷 琦，潘雅娟，宋允章，楊 謙

目的 探討幽門螺桿菌(helicobacter pylori, HP)細(xì)胞毒素相關(guān)蛋白A(cytotoxin-associated protein， CagA)與動(dòng)脈粥樣硬化性腦梗死的關(guān)系。方法 選取2015年6月—2016年11月我院收治的動(dòng)脈粥樣硬化性腦梗死患者65例作為研究對(duì)象，根據(jù)是否存在頸動(dòng)脈斑塊分為頸動(dòng)脈斑塊陽(yáng)性組(陽(yáng)性組)35例和頸動(dòng)脈斑塊陰性組(陰性組)30例；另選擇同期門診體檢健康者30例作為對(duì)照組。比較3組CagA-HP-IgG抗體陽(yáng)性率，探討陽(yáng)性組頸動(dòng)脈病變與CagA-HP-IgG抗體的相關(guān)性，分析血清CagA-HP-IgG抗體對(duì)頸動(dòng)脈病變的診斷效能。結(jié)果 陽(yáng)性組血清CagA-HP-IgG抗體陽(yáng)性率為62.9%，高于陰性組的40.0%和對(duì)照組的23.3%，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。Pearson相關(guān)檢驗(yàn)顯示，陽(yáng)性組頸動(dòng)脈病變與血清CagA-HP-IgG抗體水平呈正相關(guān)(r=0.745，P=0.024)。血清CagA-HP-IgG抗體診斷頸動(dòng)脈病變的靈敏度和特異度分別為90.5%和88.7%，受試者工作特征曲線下面積為0.938(95% CI：0.882，0.995)。結(jié)論 血清CagA-HP-IgG或可作為動(dòng)脈粥樣硬化性腦梗死患者早期診斷頸動(dòng)脈病變的一項(xiàng)檢測(cè)指標(biāo)。

幽門螺桿菌；細(xì)胞毒素相關(guān)蛋白A；動(dòng)脈粥樣硬化；腦梗死

相關(guān)研究顯示，30%～59%的腦卒中是由顱外段頸動(dòng)脈粥樣硬化性狹窄進(jìn)行性發(fā)展所引發(fā)[1-2]。隨著對(duì)動(dòng)脈粥樣硬化的深入研究，發(fā)現(xiàn)其可能是一種炎性疾病，牙齦卟啉單胞菌、肺炎衣原體、幽門螺桿菌(helicobacter pylori, HP)等均與其形成有關(guān)。近年研究顯示，細(xì)胞毒素相關(guān)蛋白A(cytotoxin-associated protein， CagA)陽(yáng)性的HP感染可能與動(dòng)脈粥樣硬化有關(guān)，能夠顯著增加發(fā)生動(dòng)脈粥樣硬化的危險(xiǎn)性[3-5]。為進(jìn)一步觀察和證實(shí)CagA陽(yáng)性的HP感染與動(dòng)脈粥樣硬化性腦梗死的關(guān)系，本研究觀察頸動(dòng)脈粥樣硬化性腦梗死患者頸部血管病變及CagA-HP-IgG抗體的關(guān)系，現(xiàn)報(bào)告如下。

1 資料與方法

1.1 對(duì)象與分組 選取2015年6月—2016年11月我院收治的頸動(dòng)脈粥樣硬化性腦梗死65例作為研究對(duì)象，其中男33例，女32例；年齡45～72(61.8±2.1)歲；中度腦梗死32例，重度腦梗死33例。根據(jù)是否存在頸動(dòng)脈斑塊分為陽(yáng)性組35例和陰性組30例，其中陽(yáng)性組男18例，女17例；平均年齡(61.6±2.2)歲。陰性組男女各15例；平均年齡(61.9±2.4)歲。另選取同期門診體檢健康者30例作為對(duì)照組，其中男女各15例；平均年齡(62.2±1.8)歲；既往無(wú)消化系統(tǒng)疾病和心腦血管疾病。3組性別、年齡等一般資料比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，具有可比性。

1.2 檢測(cè)方法 腦梗死患者于入院次日、對(duì)照組于健康體檢時(shí)采集空腹靜脈血，采用酶聯(lián)免疫吸附法檢測(cè)CagA-HP-IgG抗體，嚴(yán)格按照抗體試劑盒(上海酶聯(lián)生物科技有限公司生產(chǎn))說(shuō)明書進(jìn)行操作，正常參考值≤12 U/ml。頸動(dòng)脈斑塊采用HDI-5000彩色多普勒超聲儀進(jìn)行檢查。

1.3 觀察指標(biāo) 比較3組CagA-HP-IgG抗體陽(yáng)性率，探討陽(yáng)性組頸動(dòng)脈病變與血清CagA-HP-IgG抗體的相關(guān)性，分析血清CagA-HP-IgG抗體對(duì)頸動(dòng)脈病變的診斷效能。

2 結(jié)果

2.1 CagA-HP-IgG抗體檢測(cè) 酶聯(lián)免疫法檢測(cè)CagA-HP-IgG抗體，結(jié)果顯示陽(yáng)性組血清CagA-HP-IgG抗體陽(yáng)性率為62.9%(22/35)，陰性組陽(yáng)性率為40.0%(12/30)，對(duì)照組陽(yáng)性率為23.3%(7/30)，陽(yáng)性率比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。

2.2 頸動(dòng)脈病變與CagA-HP-IgG抗體的相關(guān)性 Pearson相關(guān)檢驗(yàn)顯示，陽(yáng)性組頸動(dòng)脈病變與血清CagA-HP-IgG抗體水平呈正相關(guān)(r=0.745，P=0.024)。

2.3 CagA-HP-IgG抗體對(duì)頸動(dòng)脈病變的診斷效能 受試者工作特征(receiver operating characteristic， ROC)曲線提示，血清CagA-HP-IgG抗體診斷頸動(dòng)脈病變的靈敏度和特異度分別為90.5%和88.7%，ROC曲線下面積為0.938(95% CI：0.882，0.995)。見圖1。

圖1 伴頸動(dòng)脈斑塊的動(dòng)脈粥樣硬化性腦梗死患者血清CagA-HP-IgG抗體受試者工作特征曲線圖

3 討論

腦梗死主要形成原因?yàn)楣跔顒?dòng)脈內(nèi)粥樣斑塊出現(xiàn)破裂，血小板聚集后形成血栓，導(dǎo)致冠狀動(dòng)脈被完全或不完全堵塞[6-7]，但具體發(fā)生機(jī)制不明[8-9]。近年來(lái)研究發(fā)現(xiàn)，炎性反應(yīng)參與了動(dòng)脈粥樣硬化的發(fā)生、發(fā)展[10]。動(dòng)脈斑塊的不穩(wěn)定性原因可能為炎性反應(yīng)的激活[11]。HP感染可致胃外或胃內(nèi)疾病，與HP基因的不同表達(dá)密切相關(guān)。當(dāng)HP基因表型為CagA-HP時(shí)可致胃外疾病，其菌株排泌的毒素經(jīng)血液循環(huán)可進(jìn)入非消化道，寄于宿主細(xì)胞中，使宿主細(xì)胞變性壞死[8]；同時(shí)毒素還可引起血流改變，容易導(dǎo)致腦血管疾病。細(xì)胞特定部位內(nèi)的CagA-HP容易被磷酸化，細(xì)胞內(nèi)信號(hào)傳導(dǎo)使細(xì)胞骨架重排、肌蛋白聚合，影響細(xì)胞凋亡；CagA-HP增加了細(xì)胞因子的產(chǎn)生與分泌，可誘使炎性反應(yīng)發(fā)生；在CagA-HP毒素的影響下，宿主細(xì)胞會(huì)凋亡或增殖[12]。

HP影響動(dòng)脈粥樣硬化形成包括免疫介導(dǎo)、自由基形成及低度急性過(guò)程反應(yīng)3種方式[13]。HP感染時(shí)機(jī)體超敏C-反應(yīng)蛋白、白細(xì)胞計(jì)數(shù)及纖維蛋白原等水平升高。當(dāng)HP持續(xù)感染時(shí)可影響胃免疫細(xì)胞產(chǎn)生大量炎性細(xì)胞因子，并激活血管內(nèi)皮細(xì)胞，影響纖維蛋白原、組織因子表達(dá)增加，隨著血液的進(jìn)一步黏稠，炎性反應(yīng)遍及全身，使某些血液成分發(fā)生改變，同時(shí)也會(huì)在斑塊覆蓋區(qū)域出現(xiàn)炎性反應(yīng)，可直接導(dǎo)致血栓形成，加重腦梗死。本結(jié)果顯示，陽(yáng)性組血清CagA-HP-IgG抗體陽(yáng)性率為62.9%顯著高于陰性組及對(duì)照組，說(shuō)明發(fā)生頸動(dòng)脈病變的腦梗死患者血清CagA-HP-IgG抗體水平增加；經(jīng)Pearson相關(guān)檢驗(yàn)顯示，陽(yáng)性組頸動(dòng)脈病變與血清CagA-HP-IgG抗體水平呈正相關(guān)；血清CagA-HP-IgG抗體診斷頸動(dòng)脈病變的靈敏度和特異度分別為90.5%和88.7%，ROC曲線下面積為0.938。提示腦梗死患者頸動(dòng)脈病變程度與血清CagA-HP-IgG抗體水平密切相關(guān)，隨著腦梗死病程的延長(zhǎng)，血清CagA-HP-IgG抗體水平增加，最終會(huì)誘發(fā)頸動(dòng)脈病變。

綜上，血清CagA-HP-IgG或可作為動(dòng)脈粥樣硬化性腦梗死患者早期診斷頸動(dòng)脈病變的檢測(cè)指標(biāo)。

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Relationship Between Helicobacter pylori and A and Atherosclerotic Cerebral Infarction

LV Jian-meng， YUAN Jie， LEI Qi， PAN Ya-juan， SONG Yun-zhang， YANG Qian

( Department of Neurology, Shaanxi Provincial People's Hospital， Xi'an 710068, China)

Objective To investigate the relationship between Helicobacter pylori (HP) cytotoxin associated protein A (CagA) and atherosclerotic cerebral infarction. Methods From June 2015 to November 2016 in our hospital 65 cases of patients with cerebral infarction as the research object, 65 patients according to carotid artery plaque positive cases divided into carotid artery plaque in patients with cerebral infarction male positive group (observation group,n=35), cerebral infarction and non carotid artery plaque group (control group,n=30). At the same time, 30 healthy persons were selected as control group. The positive rate of CagA-HP-IgG antibody was compared between the three groups, and the correlation between the carotid artery lesions and serum CagA-HP-IgG antibody in the observation group was analyzed, and the diagnostic value of serum CagA-HP-IgG antibody was analyzed. Results The observation group positive rate of serum CagA-HP-IgG antibody was 62.9%; the control group of serum CagA-HP-IgG antibody positive rate of 40.0%; the positive rate of serum CagA-HP-IgG antibody was 23.3% blank control group; three serum CagA-HP-IgG antibody positive rate difference significantly (P<0.05). The Pearson correlation test showed that the carotid artery lesions in the observation group were positively correlated with the level of serum CagA-HP-IgG antibody (r=0.745,P=0.024). The sensitivity and specificity of serum CagA-HP-IgG antibody in the diagnosis of carotid artery lesions were 90.5% and 88.7%, respectively. The area under the ROC curve was 0.938 ( 95% CI:0.882,0.995). Conclusion CagA-HP-IgG may can be used as a predictive method for early carotid artery disease in patients with atherosclerotic cerebral infarction.

Helicobacter pylori; Cytotoxin associated protein A; Atherosclerosis; Cerebral infarction

陜西省自然科學(xué)基礎(chǔ)研究計(jì)劃項(xiàng)目(2014JM4131)

710068 西安，陜西省人民醫(yī)院神經(jīng)內(nèi)二科

楊謙，E-mail：29328553@qq.com

R743.33

A

1002-3429(2017)04-0080-03

10.3969/j.issn.1002-3429.2017.04.028

2016-09-12 修回時(shí)間：2017-02-15)