本文選題：頸動脈內(nèi)膜剝脫術(shù) + 低灌注��； 參考：《河北北方學(xué)院》2014年碩士論文

【摘要】：動脈粥樣硬化導(dǎo)致的頸動脈狹窄是引起短暫腦缺血發(fā)作（transientischemia attack，TIA）和缺血性卒中的主要原因之一，頸動脈內(nèi)膜剝脫術(shù)（carotid endarterectomy，CEA）已被證實可有效解除顱外頸動脈狹窄和預(yù)防缺血性卒中。但是，CEA本身有一定的手術(shù)并發(fā)癥發(fā)生率，其中術(shù)后卒中和死亡最為嚴(yán)重。目前，尚無理想的CEA圍手術(shù)期腦缺血性損傷監(jiān)測方式，在此背景下，生化標(biāo)志物對CEA圍手術(shù)期腦缺血性損傷的預(yù)警作用越來越受到重視。目前已有部分生化標(biāo)志物被證實在卒中具有預(yù)警作用如基質(zhì)金屬蛋白酶9（matrix metalloproteinases9，MMP-9）、非對稱二甲基精氨酸（asymmetric dimethylarginine，ADMA）等，我們設(shè)想，這些生化標(biāo)志物是否在CEA圍手術(shù)期同樣具有預(yù)警腦缺血性損傷作用。 研究對象為自2012年2月至2012年9月期間在北京協(xié)和醫(yī)院血管外科行CEA治療的頸動脈狹窄患者，入組標(biāo)準(zhǔn)：同意參與本次研究并簽署知情同意書；年齡介于40-80歲；術(shù)側(cè)頸動脈狹窄≥70%；經(jīng)顱多普勒超聲（transcranial doppler sonography，TCD）監(jiān)測存在顳窗；計算機(jī)斷層掃描血管成像（computed tomography angiography，CTA）已證實術(shù)前頸動脈狹窄程度。排除標(biāo)準(zhǔn)：無顳窗，不能在CEA術(shù)中監(jiān)測大腦中動脈血流速度（middle cerebral artery velocity，MCAV）；頸動脈支架置入（carotid artery stenting，CAS）術(shù)后再狹窄；非動脈粥樣硬化性頸動脈狹窄，如大動脈炎、纖維肌性發(fā)育不良；對抗血小板和他汀類藥物過敏；拒絕簽署知情同意書。 分組方式：根據(jù)CEA術(shù)中是否有微栓子脫落，將患者分為栓子組和非栓子組；根據(jù)術(shù)中頸動脈阻斷后MCAV下降是否＞50%，將患者分為低灌注組和非低灌注組。根據(jù)入組和排除標(biāo)準(zhǔn)，最終共納入46例CEA手術(shù)患者。 入組患者在以下4個時間點分別采集大隱靜脈血5ml：1、CEA術(shù)前2h；2、阻斷開放前；3、阻斷開放后1h；4、術(shù)后12h。此操作由病房及手術(shù)室護(hù)士進(jìn)行，均使用促凝管，采集成功后室溫靜置1h，然后以3000轉(zhuǎn)/分離心10min，抽取上清并分裝至離心管，分裝完成后立即置于㧟80℃冰箱進(jìn)行保存并避免反復(fù)凍融，直至檢測。血清MMP-9、ADMA、 S100B蛋白濃度均使用酶聯(lián)免疫吸附法（enzyme linkedimmunosorbent assay，ELISA）進(jìn)行檢測。MMP-9活性使用明膠酶譜試劑盒進(jìn)行檢測（life technologies，USA）。 所有CEA均在全麻下進(jìn)行，以丙泊酚、羅庫溴銨、芬太尼/舒芬太尼進(jìn)行麻醉誘導(dǎo)，劑量根據(jù)術(shù)中需要決定，麻醉誘導(dǎo)成功后使用七氟醚吸入麻醉維持麻醉狀態(tài)。術(shù)中持續(xù)監(jiān)測心電活動、橈動脈內(nèi)血壓、動脈血氧飽和度。所有入組患者均使用TCD對整個手術(shù)過程MCAV以及微栓子信號進(jìn)行監(jiān)測。微栓子的診斷為1995年第9屆腦血流動力學(xué)會制定：（1）短暫出現(xiàn)，持續(xù)時間≤300ms；（2）信號強(qiáng)度高于背景信號至少3dB；（3）單向出現(xiàn)于血流頻譜；（4）同時出現(xiàn)聲頻異常。 入組的46例CEA手術(shù)患者一般情況為：男性36例，女性10例；年齡（63.7±9.1）歲。其中，合并術(shù)前高血壓34例，糖尿病19例，冠心病12例，高脂血癥20例,卒中發(fā)作史4例，TIA發(fā)作史12例，存在術(shù)前癥狀者（入院前180內(nèi)有卒中或TIA發(fā)作）11例。在本次研究中，至術(shù)后30天，未出現(xiàn)術(shù)后卒中或TIA發(fā)作。 按照兩種分組方式比較一般情況，組間患者在年齡、高血壓、高脂血癥、糖尿病、卒中及TIA史等方面差異無統(tǒng)計學(xué)意義。在頸動脈阻斷之前，未發(fā)生微栓子脫落。在阻斷過程中，共有14例CEA監(jiān)測到微栓子脫落。另外，19例患者出現(xiàn)了阻斷過程腦低灌注。 46例CEA血清標(biāo)本均進(jìn)行了MMP-9濃度和活性的檢測。各時間點MMP-9濃度分別為：術(shù)前：440.39±253.44ng/ml；開放前：254.17±223.30ng/ml；開放后：295.65±253.17ng/ml；術(shù)后12h：617.42±364.24ng/ml。MMP-9表達(dá)在術(shù)中表達(dá)顯著降低，而在術(shù)后表達(dá)較術(shù)前顯著升高（P＜0.05）。術(shù)前MMP-9在栓子組和非栓子組、低灌注組與非低灌注組的差異均無統(tǒng)計學(xué)意義，而在術(shù)后12h，，栓子組MMP-9顯著高于非栓子組（P＜0.05）。 在非栓子組，術(shù)前和術(shù)后MMP-9差異無統(tǒng)計學(xué)意義（術(shù)前：414.71±250.68ng/ml和術(shù)后：526.07±313.94ng/ml，P＞0.05）；在栓子組，MMP-9在術(shù)后明顯高于術(shù)前（術(shù)前：499.09±259.15ng/ml和術(shù)后826.19±395.91ng/ml，P＜0.05）。此外，所有血清標(biāo)本均使用明膠酶譜法對MMP-9活性進(jìn)行檢測，活性檢測結(jié)果同ELISA結(jié)果一致。與術(shù)前相比，術(shù)后MMP-9活性在術(shù)中微栓子脫落的病例中表達(dá)明顯升高。 在非低灌注組，術(shù)前和術(shù)后MMP-9差異無統(tǒng)計學(xué)意義（術(shù)前：447.89±261.59ng/ml和術(shù)后：589.69±326.93ng/ml，P＞0.05）；在低灌注組，MMP-9在術(shù)后高于術(shù)前且差異具有統(tǒng)計學(xué)意義（術(shù)前：429.73±248.06ng/ml和術(shù)后656.82±417.73ng/ml，P＜0.05）。 我們對其中19例CEA血清標(biāo)本進(jìn)行了檢測，患者一般情況在栓子組和非栓子組、低灌注組合非低灌注組的差異均無統(tǒng)計學(xué)意義。共計3例在術(shù)中出現(xiàn)微栓子，另有6例在阻斷中存在低灌注。各時間點ADMA濃度分別為：術(shù)前：99.12±53.63ng/ml；開放前：51.61±25.72ng/ml；開放后：88.54±30.57ng/ml；術(shù)后12h：165.02±115.80ng/ml。ADMA表達(dá)在術(shù)中表達(dá)顯著降低，而在術(shù)后其表達(dá)較術(shù)前顯著升高（P＜0.05）。無論術(shù)前或者術(shù)后，ADMA在栓子組和非栓子組、低灌注組與非低灌注組差異均無統(tǒng)計學(xué)意義。 在非栓子組，術(shù)前和術(shù)后ADMA差異具有統(tǒng)計學(xué)意義（術(shù)前：88.64±32.76ng/ml和術(shù)后：169.39±121.48ng/ml，P＜0.05）；而在栓子組，術(shù)后ADMA低于術(shù)前但未達(dá)到統(tǒng)計學(xué)差異（術(shù)前：155.01±110.79ng/ml和術(shù)后141.71±95.09ng/ml，P＞0.05）。 在非低灌注組，術(shù)前和術(shù)后ADMA差異無統(tǒng)計學(xué)意義（術(shù)前：101.40±60.69ng/ml和術(shù)后：167.82±137.15ng/ml，P＞0.05）；在低灌注組，ADMA在術(shù)后高于術(shù)前且差異具有統(tǒng)計學(xué)意義（術(shù)前：94.17±38.37ng/ml和術(shù)后158.95±55.37ng/ml，P＜0.05）。 我們對其中11例CEA血清標(biāo)本進(jìn)行了S100B檢測，其中有6例出現(xiàn)阻斷中低灌注，無微栓子脫落發(fā)生。不過，在本次研究中測得的血清S100B表達(dá)較低，其表達(dá)水平同國內(nèi)外多數(shù)文獻(xiàn)相關(guān)報道存在較大差異，且未能觀察到部分文獻(xiàn)報道的CEA術(shù)后S100B升高的現(xiàn)象，也未發(fā)現(xiàn)S100B同CEA術(shù)中腦低灌注相關(guān)。本研究中測得的各時間點S100B濃度分別為：術(shù)前：11.26±7.58pg/ml；開放前：14.55±15.93pg/ml；開放后：9.80±3.18pg/ml；術(shù)后12h：13.39±15.85pg/ml。然而，本次研究采用的S100B蛋白試劑盒檢測靈敏度為15pg/ml，因此數(shù)據(jù)可能存在較大誤差，未予采用。 我們的研究證實了CEA術(shù)后12h即可出現(xiàn)MMP-9表達(dá)升高，且同術(shù)中微栓子脫落、阻斷中腦低灌注有關(guān)，證實MMP-9可能早期發(fā)現(xiàn)CEA術(shù)后微栓子和腦低灌注相關(guān)的腦缺血性損傷的作用。本次研究中，無CEA后30天內(nèi)卒中或TIA發(fā)作，因而未能證實MMP-9是否對CEA術(shù)后卒中和TIA有預(yù)警作用。另外，ADMA同CEA阻斷中腦低灌注有關(guān)，提示ADMA可在CEA術(shù)后早期升高，且同腦缺血性損傷有關(guān)，可作為腦缺血性損傷的生化標(biāo)志物。
[Abstract]:Carotid stenosis caused by atherosclerosis is one of the main causes of transient ischemic attacks (transientischemia attack, TIA) and ischemic stroke. Carotid endarterectomy (carotid endarterectomy, CEA) has been proved to be effective in relieving the narrowing of the extracranial carotid artery and preventing ischemic stroke. However, the CEA itself has a certain hand. The incidence of postoperative complications, including death and death, is the most serious. Currently, there is no ideal method of monitoring ischemic injury in the perioperative period of CEA. In this context, the role of biochemical markers for early warning of ischemic injury in the perioperative period of CEA is becoming more and more important. Such as matrix metalloproteinase 9 (matrix Metalloproteinases9, MMP-9), asymmetric two methyl arginine (asymmetric dimethylarginine, ADMA), etc., we assume that these biochemical markers also have an early warning of ischemic brain damage during the perioperative period of CEA.
The subjects were patients with carotid stenosis treated with CEA in the Peking Union Medical College Hospital from February 2012 to September 2012. The standard of admission was to participate in the study and sign the informed consent; the age of 40-80 years old; the lateral carotid stenosis more than 70%; the transcranial Doppler ultrasound (transcranial Doppler sonography, TCD). Measuring the presence of temporal windows; computed tomography angiography (computed tomography angiography, CTA) confirmed the degree of preoperative carotid stenosis. Exclusion criteria: no temporal window and no monitoring of the middle cerebral artery blood flow velocity (middle cerebral artery velocity, MCAV) during CEA; carotid stent implantation (carotid artery) Restenosis; non atherosclerotic carotid artery stenosis, such as Takayasu's arteritis, fibrous dysplasia; antithrombotic and statin allergies; refusing to sign informed consent.
Group method: the patients were divided into embolic and non embolic groups according to whether there was a micro embolus in CEA, and whether the decrease of MCAV was > 50% after the operation of carotid artery occlusion. The patients were divided into low perfusion group and non low perfusion group. According to the entry group and the exclusion criteria, the patients were finally included in the 46 cases of CEA operation.
The patients in the group were collected at the following 4 time points to collect the great saphenous vein blood 5ml:1, CEA before operation 2H; 2, block the opening before opening; 3, block the opening after the 1H; 4, the operation of 12h. after the operation was carried out by the ward and the operation room, all using the procoagulant tube, after the successful collection of the room temperature static 1H, and then 3000 turn / separate heart 10min, extraction supernatant and sub loaded into centrifuge tube, divided into centrifuge tube. After completion of the installation, it was immediately placed in the refrigerator at 80 degrees centigrade to avoid repeated freezing and thawing until testing. The serum MMP-9, ADMA, and S100B protein concentrations were detected by enzyme linked immunosorbent assay (enzyme linkedimmunosorbent assay, ELISA) for detection of.MMP-9 activity using a gelatinase Kit (life technologies, USA).
All CEA were performed under general anesthesia with propofol, rocuronium and fentanyl / sufentanil for anesthesia induction. The dose was determined according to the needs of the operation. After anesthesia induction, sevoflurane inhalation anesthesia was used to maintain the anesthetic state. Intraoperative monitoring of electrocardiography, radial arterial blood pressure and arterial oxygen saturation were continuously monitored during the operation. All the patients were treated with TCD. MCAV and the signal of the micro embolus were monitored throughout the operation. The diagnosis of the micro embolus was made by the ninth CBD in 1995: (1) transient appearance, duration less than 300ms; (2) the signal intensity was higher than the background signal at least 3dB; (3) one direction appeared in the blood flow spectrum; (4) there was a sound frequency anomaly at the same time.
The general situation in the 46 cases of CEA surgery was 36 males and 10 females; age (63.7 + 9.1) years. Among them, 34 cases of pre operation hypertension, 19 cases of diabetes, 12 cases of coronary heart disease, 20 cases of hyperlipidemia, 4 cases of stroke history, 12 history of stroke, and 10 cases of preoperative symptoms (including stroke or TIA attack before admission) were present in this study, After 30 days after the operation, there was no postoperative stroke or TIA attack.
There was no significant difference in age, hypertension, hyperlipidemia, diabetes, stroke and TIA history in the two groups. No micro embolus occurred before the occlusion of the carotid artery. In the course of the occlusion, 14 cases of CEA monitored the detachment of the micro embolus. In addition, 19 patients had the blocking process brain. Low perfusion.
The concentration and activity of MMP-9 in 46 CEA serum specimens were detected. The concentration of MMP-9 at each time point was: preoperative: 440.39 + 253.44ng/ml; before opening: 254.17 + 223.30ng/ml; after opening: 295.65 + 253.17ng/ml; the expression of 12h:617.42 + 364.24ng/ml.MMP-9 after operation decreased significantly in the operation, and the expression was more obvious after operation than before operation. The increase (P < 0.05). Before operation, there was no significant difference in MMP-9 between the emboli group and the non emboli group. The difference between the low perfusion group and the non low perfusion group was not statistically significant, while the MMP-9 in the embolic group was significantly higher than that of the non embolic group (P < 0.05) in the postoperatively 12h.
In the non embolic group, there was no significant difference between preoperative and postoperative MMP-9 (414.71 + 250.68ng/ml and postoperative: 526.07 + 313.94ng/ml, P > 0.05), and in the embolic group, MMP-9 was significantly higher than preoperative (preoperative: 499.09 + 259.15ng/ml and 826.19 + 395.91ng/ml after operation, P < 0.05). In addition, all serum specimens were treated with gelatinase method to M The activity of MP-9 was detected, and the result of activity test was consistent with that of ELISA. The expression of MMP-9 increased significantly in the case of microemboli after operation.
In the non low perfusion group, there was no significant difference between preoperative and postoperative MMP-9 (preoperative: 447.89 + 261.59ng/ml and postoperative: 589.69 + 326.93ng/ml, P > 0.05). In the low perfusion group, MMP-9 was higher than preoperative and the difference was statistically significant (429.73 + 248.06ng/ml and 656.82 + 417.73ng/ml after operation, P < 0.05).
We examined 19 CEA serum specimens. There were no significant differences between the patients in the emboli group and the non embolic group. The difference in the low perfusion group was not statistically significant. A total of 3 cases had micro embolus and 6 cases had low perfusion in the occlusion. The concentration of ADMA at each time point was 99.12 + 53.63ng/ml before operation, respectively. Pre release: 51.61 + 25.72ng/ml, after opening: 88.54 + 30.57ng/ml, the expression of 12h:165.02 + 115.80ng/ml.ADMA after operation was significantly lower, and the expression was significantly higher than before operation (P < 0.05). No matter before or after the operation, there was no statistical difference between the low perfusion group and the non low perfusion group, both in the emboli group and in the non embolic group.
In the non embolic group, the preoperative and postoperative ADMA differences were statistically significant (preoperative: 88.64 + 32.76ng/ml and postoperative: 169.39 + 121.48ng/ml, P < 0.05), but in the embolic group, ADMA was lower than preoperative but not statistically significant (preoperative: 155.01 + 110.79ng/ml, 141.71 + 95.09ng/ml, P > 0.05).
In the non low perfusion group, there was no significant difference between preoperative and postoperative ADMA (preoperative: 101.40 + 60.69ng/ml and postoperative: 167.82 + 137.15ng/ml, P > 0.05). In the low perfusion group, ADMA was higher than preoperative and the difference was statistically significant (94.17 + 38.37ng/ml and 158.95 + 55.37ng/ml after operation, P < 0.05).
11 of the CEA serum samples were detected by S100B, of which 6 cases were blocked by middle and low perfusion and no micro emboli occurred. However, the serum S100B expression was low in this study, and the expression level was very different from most of the literature related reports in and outside the country, and there was no observation of S100 after the CEA operation reported in some literature. The phenomenon of B elevation was not found to be associated with cerebral hypoperfusion in CEA. The concentration of S100B at each time point in this study was: 11.26 + 7.58pg/ml before operation, 14.55 + 15.93pg/ml before opening, 9.80 + 3.18pg/ml after opening, and 12h:13.39 + 15.85pg/ml. after operation, however, the S100B protein kits used in this study were detected in this study. The sensitivity is 15pg/ml, so the data may have large errors and have not been adopted.
Our study confirmed that the increase of MMP-9 expression in 12h after CEA was associated with the abscission of the microembolus in the operation and the blocking of the hypoperfusion of the midbrain. It was confirmed that MMP-9 may early detect the ischemic damage of the microembolus and cerebral hypoperfusion after CEA. In this study, there was no stroke or TIA seizures within 30 days after CEA, and thus failed to confirm that MMP-9 was There is an early warning effect on stroke and TIA after CEA. In addition, ADMA is associated with CEA blocking the middle cerebral hypoperfusion, suggesting that ADMA can be raised early after CEA and is associated with cerebral ischemic injury, which can be used as a biochemical marker for cerebral ischemic injury.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R743.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 Jian Zhang;Dan Zhang;Guo-Qing Wu;Zhi-Ying Feng;Sheng-Mei Zhu;;Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression[J];Hepatobiliary & Pancreatic Diseases International;2013年03期

2 牛宏珍;勇強(qiáng);張蕾;秋陽;李春梅;張爽;張勤奕;何曉芬;李同勛;;彩色多普勒超聲在頸動脈內(nèi)膜剝脫術(shù)中的應(yīng)用[J];中國介入影像與治療學(xué);2012年12期

3 陶定波;姜秀麗;雷陽;洪曉軍;孫大勇;;血清基質(zhì)金屬蛋白酶9和組織基質(zhì)金屬蛋白酶抑制劑1與急性腦梗死的臨床關(guān)系[J];中華老年心腦血管病雜志;2009年10期

本文編號：2007501