目的:观察症状性颈动脉重度狭窄患者支架成形术后血清IL-6、IL-8、IL-10和TNF-α表达水平的动态变化并探讨其临床意义。方法:选择2018年08月至2022年08月于我院神经介入科住院治疗的112例症状性颈动脉重度狭窄患者作为研究对象。依据手术方式的不同,分为单纯造影组45例;支架成形术组67例。对支架成形术组患者,依据术后3 d颅脑DWI-MRI检查结果判断是否发生颅内微缺血(IMI),分为微缺血组29例和无微缺血组38例。检测所有患者手术前和术后24 h、3 d、30 d血清IL-6、IL-8、IL-10和TNF-α表达水平,观察患者手术前后炎症因子动态变化情况,比较微缺血组与无微缺血组炎症反应的差别。结果:与单纯造影组相比,支架成形术组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α表达水平均显著增高(P < 0.05)。与术前相比,支架成形术组患者术后24 h血清IL-6、IL-8、IL-10和TNF-α水平显著升高(P < 0.05),并达到高峰,术后30 d血清IL-6、IL-8、IL-10和TNF-α水平恢复至术前水平。微缺血组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α表达水平显著高于无微缺血组(P < 0.05)。结论:症状性颈动脉重度狭窄患者支架成形术后发生了急性血管炎症反应,术后发生微缺血事件患者的血管炎症反应较未发生者更为强烈。 Objective: To observe the dynamic changes of serum levels of IL-6, IL-8, IL-10 and TNF-α in patients with symptomatic severe carotid artery stenosis after stenting and explore their clinical signifi-cance. Methods: A total of 112 patients with symptomatic severe carotid artery stenosis who were hospitalized in the neurointerventional department of our hospital from August 2018 to August 2022 were selected as the study objects. According to the different surgical methods, 45 cases were divided into angiography group. The stenting group was 67 cases. The patients in the stenting group were divided into 29 patients in the microischemia group and 38 patients without micro-ischemia group according to the results of postoperative 3 d head DWI-MRI examination. The ex-pression levels of IL-6, IL-8, IL-10 and TNF-α in serum were detected before and 24 h, 3 d and 30 d after surgery. The dynamic changes of inflammatory factors were observed before and after surgery, and the difference of inflammatory response between the micro-ischemia group and the non-micro-ischemia group was compared. Results: Compared with angiography group, the expres-sion levels of IL-6, IL-8, IL-10 and TNF-α in serum in stenting group were significantly increased 24 h and 3 d after stenting (P < 0.05). Compared with the preoperative level, the serum levels of IL-6, IL-8, IL-10 and TNF-α in the stent-plasty group were significantly increased 24 h after surgery and reached a peak (P < 0.05), and the serum levels of IL-6, IL-8, IL-10 and TNF-α were restored to the preoperative level 30 days after surgery. The expression levels of IL-6, IL-8, IL-10 and TNF-α in se-rum in the microischemia group were significantly higher than those in the non-microischemia group 24 h and 3 d after surgery (P < 0.05). Conclusions: Acute vascular inflammation occurred in patients with symptomatic severe carotid artery stenosis after stenting, and the vascular inflamma-tion was more intense in patients with postoperative micro ischemia events than those without.
目的:观察症状性颈动脉重度狭窄患者支架成形术后血清IL-6、IL-8、IL-10和TNF-α表达水平的动态变化并探讨其临床意义。方法:选择2018年08月至2022年08月于我院神经介入科住院治疗的112例症状性颈动脉重度狭窄患者作为研究对象。依据手术方式的不同,分为单纯造影组45例;支架成形术组67例。对支架成形术组患者,依据术后3 d颅脑DWI-MRI检查结果判断是否发生颅内微缺血(IMI),分为微缺血组29例和无微缺血组38例。检测所有患者手术前和术后24 h、3 d、30 d血清IL-6、IL-8、IL-10和TNF-α表达水平,观察患者手术前后炎症因子动态变化情况,比较微缺血组与无微缺血组炎症反应的差别。结果:与单纯造影组相比,支架成形术组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α表达水平均显著增高(P < 0.05)。与术前相比,支架成形术组患者术后24 h血清IL-6、IL-8、IL-10和TNF-α水平显著升高(P < 0.05),并达到高峰,术后30 d血清IL-6、IL-8、IL-10和TNF-α水平恢复至术前水平。微缺血组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α表达水平显著高于无微缺血组(P < 0.05)。结论:症状性颈动脉重度狭窄患者支架成形术后发生了急性血管炎症反应,术后发生微缺血事件患者的血管炎症反应较未发生者更为强烈。
颈动脉狭窄,血管成形术,炎症因子,支架成形术
Jie Ni1, Wenhui Teng2, Xianjun Zhang2, Mingyu Zhang1, Longlong Han1, Naidong Wang2*
1Department of General Medicine, The Affiliated Hospital of Qingdao University, Qingdao Shandong
2Department of Neurological Intervention, The Affiliated Hospital of Qingdao University, Qingdao Shandong
Received: Oct. 21st, 2022; accepted: Nov. 15th, 2022; published: Nov. 24th, 2022
Objective: To observe the dynamic changes of serum levels of IL-6, IL-8, IL-10 and TNF-α in patients with symptomatic severe carotid artery stenosis after stenting and explore their clinical significance. Methods: A total of 112 patients with symptomatic severe carotid artery stenosis who were hospitalized in the neurointerventional department of our hospital from August 2018 to August 2022 were selected as the study objects. According to the different surgical methods, 45 cases were divided into angiography group. The stenting group was 67 cases. The patients in the stenting group were divided into 29 patients in the microischemia group and 38 patients without microischemia group according to the results of postoperative 3 d head DWI-MRI examination. The expression levels of IL-6, IL-8, IL-10 and TNF-α in serum were detected before and 24 h, 3 d and 30 d after surgery. The dynamic changes of inflammatory factors were observed before and after surgery, and the difference of inflammatory response between the micro-ischemia group and the non-micro-ischemia group was compared. Results: Compared with angiography group, the expression levels of IL-6, IL-8, IL-10 and TNF-α in serum in stenting group were significantly increased 24 h and 3 d after stenting (P < 0.05). Compared with the preoperative level, the serum levels of IL-6, IL-8, IL-10 and TNF-α in the stent-plasty group were significantly increased 24 h after surgery and reached a peak (P < 0.05), and the serum levels of IL-6, IL-8, IL-10 and TNF-α were restored to the preoperative level 30 days after surgery. The expression levels of IL-6, IL-8, IL-10 and TNF-α in serum in the microischemia group were significantly higher than those in the non-microischemia group 24 h and 3 d after surgery (P < 0.05). Conclusions: Acute vascular inflammation occurred in patients with symptomatic severe carotid artery stenosis after stenting, and the vascular inflammation was more intense in patients with postoperative micro ischemia events than those without.
Keywords:Carotid Artery Stenosis, Angioplasty, Inflammatory Factor, Stenting
Copyright © 2022 by author(s) and Hans Publishers Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
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缺血性脑卒中约占全部卒中人群的80%,其中约20%的缺血性脑卒中起源于颈动脉斑块,颈动脉狭窄是发生脑卒中事件的主要原因 [
颈动脉支架成形术是积极预防颈动脉狭窄患者发生缺血性卒中的有效治疗方式之一,随着神经介入技术及设备的发展,颈动脉支架成形术现已具有良好的安全性,虽然术中使用的远端脑保护装置(embolic protection device, EPD)可以回收血管壁脱落的斑块,降低围手术期卒中的发生率,但一些微小斑块或血栓仍会造成患者术后颅内微缺血(intracranial micro-ischemia, IMI)的发生 [
基于上述现状,我们选取症状性颈动脉重度狭窄患者,观察支架成形术后患者血清炎症因子IL-6、IL-8、IL-10和TNF-α表达水平的动态变化情况,评估术后血管急性炎症反应并分析其临床意义。
1) 患者经脑动脉造影确诊为颈动脉重度狭窄(采用NASCET标准评价颈动脉狭窄程度为70%~99%);2) 患者TOAST病因分型为大动脉粥样硬化(LAA)型;3) 患者年龄为50~80岁;4) 单纯造影组患者仅行脑动脉造影术,患者或家属拒绝行颈动脉支架成形术治疗;5) 此研究经青岛大学附属医院道德伦理委员会审核批准,患者或家属均已签署知情同意书。
1) 无症状重度狭窄患者;2) 3个月内有颅内出血患者;3) 2周内曾发生过心肌梗死或大面积脑梗死患者;4) 重要脏器如心、肺、肝或肾等严重功能不全患者;5) 对造影剂过敏或对肝素、抗血小板类等药物存在禁忌症患者。
依据以上纳排标准,选择2018年08月至2022年08月于我院神经介入科住院治疗的症状性颈动脉重度狭窄患者112例,包括男性63例(56.25%),女性49例(43.75%);年龄58~79岁,平均(66.90 ± 4.92)岁;吸烟史38例(33.93%),糖尿病49例(43.75%),高血压病74例(66.07%);根据手术方式的不同,分为单纯造影组45例,支架成形术组67例。如表1所示,将所有患者上述各项临床基线资料进行比较,分析结果显示各组基线资料差异均无统计学意义(P > 0.05)。
项目 | 单纯造影组(n = 45) | 支架成形术组(n = 67) | F/χ2值 | P值 |
---|---|---|---|---|
性别[例(%)] | 0.066 | 0.798 | ||
男 | 26 (57.78) | 37 (55.22) | ||
女 | 19 (42.22) | 30 (44.78) | ||
年龄( x ¯ ± s ,岁) | 67.22 ± 4.61 | 66.68 ± 5.33 | 0.421 | 0.675 |
BMI ( x ¯ ± s , Kg/m2) | 24.68 ± 2.93 | 23.57 ± 2.62 | 1.399 | 0.168 |
LDL-C ( x ¯ ± s , mmol/L) | 2.19 ± 0.88 | 2.08 ± 0.79 | 0.466 | 0.643 |
吸烟史[例(%)] | 14 (31.11) | 24 (35.82) | 0.219 | 0.640 |
糖尿病[例(%)] | 19 (42.22) | 30 (44.78) | 0.041 | 0.839 |
高血压病[例(%)] | 28 (62.22) | 46 (68.66) | 2.107 | 0.147 |
表1. 单纯造影组与支架成形术组患者临床基线资料对比
注:BMI:Body Mass Index,体重指数;LDL-C:low-density lipoprotein cholesterol,低密度脂蛋白胆固醇。
单纯造影组及支架成形术组患者均于手术日当天及术后24 h、3 d、30 d采集清晨空腹肘静脉血。
患者行手术室常规术前准备,取仰卧位,行常规双侧股动脉区域消毒、铺巾,抽取2%利多卡因行右侧股动脉周围局部浸润麻醉,应用改良的Seldinger法行股动脉穿刺,置入6 F导管短鞘,透视下经导管鞘小心送入4 F单弯导管,常规依次行主动脉弓及全脑血管造影,术中应用肝素确保患者的活化凝血时间控制在150~200 S之间。
行支架成形术患者经消毒、铺巾、局部麻醉,造影过程同单纯造影组患者。然后由手术经验丰富的术者经股动脉穿刺点置换8 F动脉长鞘,配合单弯导管将中间导管选入患侧颈总动脉,然后将预选脑保护装置小心通过狭窄段血管并稳定于远端血管。造影明确责任血管具体部位及狭窄程度后,于路径图下,利用同轴技术沿导丝小心送入预选支架并释放;再次造影示血管成形良好、血流通畅者,撤出血管内治疗器械,股动脉穿刺点加压包扎,手术结束。
所有手术患者平车安返病房后,绝对卧床24 h。对于支架成形术组患者给予24 h心电血压监护,确保患者收缩压 ≤ 120 mmHg,预防术后高灌注的发生。该组患者于术后3天行颅脑DWI-MRI检查。
研究对象血清炎症因子的检测采用酶联免疫吸附法(ELISA)进行检测(试剂盒购自青岛瑞斯凯尔生物科技有限公司),严格参照试剂盒说明书进行检测。
采用SPSS 26.0统计软件进行统计学分析,正态分布的计量资料,以均数 ± 标准差( x ¯ ± s )表示,手术前后的比较采用配对样本的t检验,两组间的比较采用两独立样本的t检验。计数资料则以n (%)的形式表示,采用χ2检验或Fisher 确切概率法。P < 0.05被认为差异有统计学意义。
如表2所示,与单纯造影组相比,支架成形术组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α水平均显著增高(P < 0.05);两组患者术前及术后30 d血清炎症因子水平无明显差异(P > 0.05)。与术前相比,支架成形术组患者术后24 h血清IL-6、IL-8、IL-10和TNF-α水平显著升高(P < 0.05),并达到高峰,术后30 d血清IL-6、IL-8、IL-10和TNF-α水平恢复至术前水平。单纯造影组患者术前及术后血清炎症因子水平无明显差异(P > 0.05)。
支架成形术组患者依据术后3天颅脑DWI-MRI检查,由同一位经验丰富的影像科医师判断是否发生颅内微缺血(IMI),分为微缺血组29例和无微缺血组38例。如表3所示,微缺血组患者术后24 h、3 d血清IL-6、IL-8、IL-10和TNF-α表达水平显著高于无微缺血组(P < 0.05);两组患者术前及术后30 d血清炎症因子水平无明显差异(P > 0.05)。
组别 | 术前 | 术后24 h | 术后3 d | 术后30 d |
---|---|---|---|---|
单纯造影组 | ||||
IL-6 (pg/ml) | 3.55 ± 0.35 | 3.61 ± 0.62 | 3.53 ± 0.41 | 3.49 ± 0.76 |
IL-8 (pg/ml) | 14.12 ± 1.37 | 14.35 ± 1.49 | 14.13 ± 2.09 | 14.27 ± 1.21 |
IL-10 (pg/ml) | 9.05 ± 1.05 | 8.99 ± 1.78 | 9.26 ± 1.93 | 9.13 ± 1.42 |
TNF-α (pg/ml) | 10.89 ± 1.28 | 10.51 ± 2.93 | 10.36 ± 2.72 | 10.56 ± 1.26 |
支架成形术组 | ||||
IL-6 (pg/ml) | 3.59 ± 0.41 | 16.05 ± 1.42a b | 10.32 ± 2.41a b | 3.57 ± 0.73 |
IL-8 (pg/ml) | 14.17 ± 1.34 | 20.11 ± 3.03a b | 17.17 ± 2.45a b | 14.26 ± 1.62 |
IL-10 (pg/ml) | 9.11 ± 1.57 | 16.03 ± 1.62a b | 13.21 ± 1.35a b | 9.07 ± 1.81 |
TNF-α (pg/ml) | 10.26 ± 1.15 | 21.82 ± 2.44a b | 15.46 ± 2.78a b | 10.44 ± 1.05 |
表2. 单纯造影组与支架成形术组患者手术前后血清炎症因子表达水平的比较( x ¯ ± s )
注:a与单纯造影组同时间点比较,P < 0.05;b与同组术前比较,P < 0.05。
组别 | 术前 | 术后24 h | 术后3 d | 术后30 d |
---|---|---|---|---|
无微缺血组 | ||||
IL-6 (pg/ml) | 3.53 ± 0.56 | 13.94 ± 2.15 | 8.21 ± 1.74 | 3.59 ± 0.31 |
IL-8 (pg/ml) | 14.15 ± 1.62 | 17.57 ± 2.27 | 16.07 ± 2.94 | 14.21 ± 1.88 |
IL-10 (pg/ml) | 9.12 ± 0.83 | 13.41 ± 2.43 | 12.51 ± 2.54 | 9.04 ± 1.12 |
TNF-α (pg/ml) | 10.14 ± 2.35 | 19.03 ± 1.61 | 13.71 ± 2.48 | 10.51 ± 1.14 |
微缺血组 | ||||
IL-6 (pg/ml) | 3.67 ± 0.24 | 18.81 ± 2.92c | 13.08 ± 1.59c | 3.54 ± 0.28 |
IL-8 (pg/ml) | 14.20 ± 1.67 | 23.44 ± 3.54c | 18.61 ± 2.78c | 14.33 ± 1.52 |
IL-10 (pg/ml) | 9.10 ± 0.97 | 19.46 ± 2.96c | 14.12 ± 2.15c | 9.15 ± 1.17 |
TNF-α (pg/ml) | 10.42 ± 1.04 | 25.45 ± 3.52c | 17.75 ± 1.94c | 10.34 ± 1.64 |
表3. 微缺血组和无微缺血组患者血清炎症因子表达水平的比较( x ¯ ± s )
注:c与无微缺血组同时间点比较,P < 0.05。
颈动脉粥样硬化性狭窄最常见发生在颈内动脉和颈外动脉的分叉处 [
颈动脉狭窄患者行血管成形术过程中会造成血管壁的机械性损伤,受损的血管内皮将会发生免疫细胞的炎性浸润及炎症因子分泌增加 [
本研究旨在观察症状性颈动脉重度狭窄患者在支架成形术破坏斑块稳定性之后血清炎症因子的动态变化情况。与既往研究一致,本研究发现支架成形术组患者术后24 h血清IL-6、IL-8、IL-10和TNF-α水平显著升高,并且达到高峰(P均 < 0.05),术后3 d血清炎症因子表达水平有所下降,术后30 d血清炎症因子水平恢复至术前水平。这说明支架成形术后颈动脉狭窄患者出现了血管的急性炎症反应,提示支架置入血管过程中会损伤粥样硬化斑块,激活炎症反应,触发炎症因子IL-6、IL-8、IL-10和TNF-α的高表达。支架本身作为一种外来物也可能诱导患者体内多种炎症因子的表达与释放,促进患者炎症反应,刺激血管内膜的增生。
颈动脉支架成形术后出现的颅内微缺血灶是常见术后并发症,Cho等人的研究得出颈动脉支架成形术后出现颅内微缺血的概率为37.4% [
本研究为单中心的临床研究,样本量有限,因此结论存在一定的局限性,仍有待更大规模的多中心研究进一步验证。
倪 杰,滕文慧,张贤军,张铭宇,韩龙龙,王乃东. 症状性颈动脉重度狭窄患者支架成形术后血清炎症因子的变化及临床意义Changes and Clinical Significance of Serum Inflammatory Factors in Patients with Symptomatic Severe Carotid Artery Stenosis after Stenting[J]. 临床医学进展, 2022, 12(11): 10639-10645. https://doi.org/10.12677/ACM.2022.12111532