炎症与动脉粥样硬化沈 彬 综述 吴宗贵 审校(第二军医大学长征医院心血管内科, 上海 200003)Inflamm ation and AtherosclerosisSHEW Bin, WU Zong2gui(Depart ment of Cardiology,The Changz heng Hospital of Second Military Medical U niversity, S hanghai 200003, China)文章编号:100423934(2004)0120066204 中图分类号:R543.5 文献标识码:A 摘要: 冠状动脉粥样硬化是冠心病的病理基础,近年来的研究表明,炎症在动脉粥样硬化(AS)斑块的发生、演变及破裂过程中有至关重要的作用。
本文主要对炎症反应在AS的触发因素、可能的调控机制及血清学标志物、抗炎治疗等方面在近年来的研究进展作一综述。
关键词:动脉粥样硬化;冠心病;炎症反应 目前认为,Ross的“炎症假说”是AS的主要发病机制,也有人提出AS是一种自身免疫性疾病,AS病变与多种自身免疫性疾病如类风湿关节炎及系统性硬化有诸多相似之处,AS的某些危险因素如氧化的低密度脂蛋白、微生物抗原及热休克蛋白可诱发血管壁的免疫反应,认为炎症和免疫反应是内在和外在的危险因素,从而导致AS发病。
现将近年来有关炎症与AS 发病机制的研究情况作一综述。
1 AS炎症假说[1]此假说要点主要有:(1)AS是脂质沉积于动脉壁形成局部斑块的过程,此过程经由炎症反应介导;(2)此炎症反应的特点是:出现单核/巨噬细胞、活化T细胞和纤维化,分布尤其多见于血管分支及流出口;抗体及细胞免疫应答二者都能调控炎症反应及AS的发生与发展;(3)AS的破裂造成血栓,形成急性冠脉综合征(ACS),其过程也有大量炎性细胞和炎性介质的参与。
2 触发AS炎症反应的因素AS病变是炎症分子和细胞间的一系列反应,然而触发及促进此炎症反应的刺激因子是什么至今仍不明确,目前研究认为有以下一些因素的参与。
•临床论著•外周血炎症细胞因子与脑动脉粥样硬化性狭窄的关系黄双娇 马晓明 盛世英 苑杰 张江 刘猛 岳春贤*【摘要】目的探讨外周血炎症细胞因子与脑动脉粥样硬化性狭窄（cerebral atherosclerotic stenosis，CAS）的相关性。
方法 以2021年6月- 2023年3月医院收治的急性脑梗死患者和脑小血管病患者为调查对象，根据头颅MRA/CTA和DSA检查结果将患者分为CAS组（病例组）和血管正常组（对照组）。
采用酶联免疫吸附法对血清细胞因子进行检测，比较各细胞因子在两组间分布情况。
采用多因素Logistic回归分析分析各因素与CAS的关系，并采用ROC曲线分析各因子水平对CAS的诊断效果。
结果 本研究共纳入95名患者，单因素分析显示，卒中史、白细胞介素-2（IL-2）、肿瘤坏死因子-α （TNF-α）、肿瘤坏死因子-γ（TNF-γ）与CAS有关（P<0.05）。
多因素Logistic回归分析结果表明IL-2（OR=1.083；95％CI: 1.004～1.167，P=0.038）、TNF-α（OR=1.076；95％CI: 1.009～1.147，P=0.025）与脑动脉粥样硬化性狭窄有关。
ROC曲线分析显示，IL-2在13.08时（AUC=0.726，95%CI: 0.623～0.828, P<0.001）、TNF-α在12.78时（AUC=0.683，95%CI=0.577～0.789,P=0.002）有一定的诊断效能，但诊断的灵敏度较低（<50%）,漏诊率较高。
结论 血清中IL-2、TNF-α水平与脑动脉粥样硬化性血管狭窄有关，当血清中IL-2、TNF-α水平升高，发生脑动脉粥样硬化性血管狭窄的危险性增大。
【关键词】 脑动脉粥样硬化性狭窄；脑梗死；炎症细胞因子；脑小血管病中图分类号 R743.1文献标识码 A 文章编号1671-0223(2023)22-1681-04Correlation analysis of inflammatory cytokines and cerebral arteriosclerosis stenosis Huang Shuangjiao, Ma Xiaoming, Sheng Shiying, Yuan Jie, Zhang Jiang, Liu Meng, Yue Chunxian. The First People's Hospital of Changzhou, Changzhou 213003, China【Abstract】Objective To investigate the relationship between inflammatory cytokines and cerebral atheroscleroticstenosis (CAS). Methods Patients with cerebral small vessel disease or acute infarction were collected from 2021.6to 2023.3. Patients were divided into CAS group and normal vessel group according to MRA/CTA or DSA. Serum cytokines were measured by ELISA and the distribution of cytokines was compared between the two groups. Logistic regression analysis and ROC curve were used to judge the predictive value. Subgroup analysis was performed to comparethe distribution of cytokines in different vascular conditions according to the presence of acute cerebral infarction. Multivariate logistic regression analysis was used to analyze the relationship between each factor and CAS, and ROCcurve was used to analyze the diagnostic effect of each factor level on CAS. Results A total of 95 patients wereincluded in this study, and multivariate analysis showed that stroke history, interleukin-2 (IL-2), tumor necrosis factor-α(TNF-α), tumor necrosis factor-γ (TNF-γ) were associated with CAS (P<0.05). The results of multivariate logistic regression analysis showed that IL-2 (OR=1.083; 95%CI: 1.004~1.167, P=0.038) and TNF-α (OR=1.076; 95%CI:1.009~1.147, P=0.025) were associated with cerebral atherosclerotic stenosis. ROC curve analysis showed that IL-2 hadcertain diagnostic efficacy at 13.08 (AUC=0.726, 95%CI: 0.623~0.828, P<0.001) and TNF-α at 12.78 (AUC=0.683,95%CI=0.577~0.789, P=0.002), but the diagnostic sensitivity was low (<50%), and the missed diagnosis rate was high. Conclusion The levels of IL-2 and TNF-α in serum are related to cerebral atherosclerotic vascular stenosis, and when thelevels of IL-2 and TNF-α in serum increase, the risk of cerebral atherosclerotic vascular stenosis increases.【Key words】 Cerebral atherosclerotic stenosis; Inflammatory cytokines; Cerebral infarction; Cerebral small vesseldisease基金项目：河北省科技计划项目(编号：152777175)；江苏省常州市科技计划资助项目(编号：CJ20220201)作者单位：213003 江苏省常州市第一人民医院神经内科（黄双娇、盛世英、刘猛、岳春贤）；华北理工大学（马晓明）；华北理工大学精神卫生研究所（苑杰）；华北理工大学附属医院（张江）* 通讯作者在不良生活方式和不断严重的人口老龄化问题影响下，脑卒中已成为越来越常见的神经系统疾病，而这其中 65%～80%的患者表现为缺血性卒中[1]。
动脉粥样硬化炎症相关信号转导通路的研究进展动脉粥样硬化（AS）是各种心脑血管疾病的病理基础，严重威胁着人类的健康，近年来炎症学说受到了越来越多学者的重视，从抗炎及免疫调节角度探讨抗AS是一种新思路，在炎症演变过程中，有多条信号通路参与其中，深入研究信号通路，有望成为动脉粥样硬化药物研究干预靶点。
本文从分子生物学水平总结前瞻性的基础研究进展，以期给AS及其相关疾病的治疗带来启发。
[Abstract] Atherosclerosis （AS）is the pathological basis of cardiovascular disease，which is a serious threat to human health. In recent years，more and more scholars pay attention to the theory of inflammation. It is a new idea to treat AS from the point of view with antiinflammation and immunoregulation. There are multiple signal transduction pathways involved in the course of inflammation progress. The signaling pathway is studied deeply that is expected to become a target for intervention of atherosclerosis drugs. This article summerizes the prospective basic experimental from cellular and molecular level，to bring about inspiration in the treatment of AS and AS related diseases.[Key words] Atherosclerosis；Cardiovascular disease；Inflammation theory；Signaling pathway随着我国人口老龄化进程的加快，动脉粥样硬化（AS）性心脑血管疾病的发病率及死亡率呈现上升趋势，约有1000多万人死于AS所引起的心脑血管疾病，为此深入研究AS发病机制尤为关键。
