斑块内血管生成在兔动脉粥样硬化斑块发生发展中的作用

目的观察斑块内血管生成对兔动脉粥样硬化斑块形成与发展的影响。方法用高胆固醇饲料复制动脉粥样硬化兔模型。15只日本大耳白兔随机分为3组:A组,阴性对照组,仅给普通饲料喂养,B、C组给高胆固醇饲料喂养3周,A组及B组肌注白蛋白(2μg/kg)(0d),C组肌注血管内皮生长因子(VEGF1652μg/kg),继续以前饲养方式3周处死动物,截取胸主动脉进行计量组织学及免疫组织化学分析,测定不同组别不同时间点兔血清白细胞介素8(IL8)浓度和血脂浓度。结果(1)斑块面积(A组0,B组1.81%±0.61%,C组24.12%±3.58%)、斑块周径(A组0,B组6.05%±1.62%,C组25.71%±1.97%)及斑块的最大厚度(A组0,B组0.06mm±0.002,C组0.16mm±0.007mm),各组间比较有显著差异(P<0.05)。(2)新生血管的密度(CD34阳性细胞数细胞数/mm2(cells/mm2)A组0,B组12.35±2.02,C组61.15±7.55)各组之间比较有显著差异(P<0.05)。(3)电镜显示:新生血管与动脉粥样斑块相邻,新生血管腔内可见淋巴细胞。(4)血清IL8浓度(+21d时A组[0.05±0.006]pg/ml,B组[0.808±0.308]pg/ml,C组[15.72±4.31]pg/ml)各组间相比有显著差异。(5)此时血清胆固醇浓度B,C两组相比无显著差异。结论斑块内血管生成是动脉粥样斑块的重要病理特征,这个过程可能与炎性反应有关。     

肺炎衣原体感染对C57BL/6J小鼠动脉粥样硬化形成的影响

目的:研究肺炎衣原体(CP)感染对C57BL/6J小鼠动脉粥样硬化(AS)形成的影响。方法:48只8周龄雄性C57BL/6J小鼠分为感染-高脂组、高脂组和感染组和对照组,喂养40周,取主动脉根部标本分析AS斑块面积,采用直接免疫荧光法检查血管壁CP抗原,微量免疫荧光法(Micro-IFA)检测CP特异性抗体IgG。结果:感染-高脂组小鼠平均AS斑块面积较高脂组增大[(135249±43748)μm2∶(96378±30945)μm2,P<0·05],感染组和对照组小鼠无AS样斑块形成。结论:CP感染可加速高脂饮食C57BL/6J小鼠的主动脉AS发展。     

粥样斑块发生发展过程中炎症和新生内膜血管之间的关系

目的为研究在控制炎症水平的情况下内膜新生血管在动脉粥样斑块发生、发展中所起到的具体作用。方法高脂饮食8周造成大鼠动脉粥样硬化（AS）模型,然后使用阿司匹林抑制AS大鼠的基础炎症水平,分别给予内皮抑素和血管内皮生长因子165（VEGF165）两种不同方法处理大鼠,8周后比较血脂、胸主动脉形态学、以及检测CD31表达水平以计算内膜新生血管的数量。结果模型组的血脂水平高于空白对照组（P<0.05）;粥样斑块内部的新生血管数量VEGF165+阿司匹林组>单纯模型对照组>阿司匹林组>内皮抑素+阿司匹林组>空白对照组（P<0.05）;阿司匹林组、内皮抑素+阿司匹林组和VEGF165+阿司匹林组的内膜面积/中膜面积的比值（IA/MA）差异无显著性,但高于单纯模型对照组（P<0.05）。结论在用阿司匹林抑制AS模型大鼠基础炎症的情况下,VEGF165和内皮抑素对血管内膜生成的影响无显著差异。     

普罗布考对兔动脉粥样硬化模型C反应蛋白水平的影响及其与斑块稳定性的关系

目的观察兔动脉粥样硬化(AS)模型中C反应蛋白(CRP)的水平与斑块稳定性之间的关系,及普罗布考对CRP水平的影响。方法 20只新西兰大白兔采用随机数字表法分为正常对照组(n=6)、高脂饮食组(n=8)和普罗布考组(n=6)。对照组予普通饲料喂养,高脂饮食组和普罗布考组予高脂饲料喂养。4周后高脂饮食组和普罗布考组行髂动脉内膜球囊损伤术。术后普罗布考组每只大白兔加用普罗布考1g/d口服,10周末取血测血清CRP水平,之后处死动物取损伤处动脉,用HE染色观察动脉病理形态学变化。结果高脂饮食组动脉可见典型的AS斑块形成,普罗布考组无典型斑块形成,内膜增厚较为明显;与高脂饮食组比较,普罗布考组血清CRP水平较低[(8.10±1.02)mg/L比(11.35±2.32)mg/L,P<0.05]。结论 CRP在兔AS模型的表达水平明显增加,与斑块的不稳定性有关,普罗布考有一定的抑制兔AS模型血清CRP表达的作用。     

血管内皮生长因子165对实验性兔动脉粥样硬化斑块形成的影响

目的观察血管内皮生长因子165对动脉粥样硬化斑块形成与发展的影响。方法利用高胆固醇饲料复制动脉粥样硬化兔模型。15只兔随机分为正常对照组、高胆固醇组和血管内皮生长因子组。42天时处死动物,截取胸主动脉进行计量组织学及免疫组织化学分析。结果正常对照组、高胆固醇组和血管内皮生长因子组的斑块面积(0%比1.81%±0.61%比24.12%±3.58%)、斑块周径(0比6.05%±1.62%比25.71%±1.97%)以及斑块最大厚度(0比0.06mm±0.002mm比0.16mm±0.007mm)均存在显著差异(P<0.05)。3组CD34阳性细胞数(cellsmm2)分别为0、12.35±2.02和61.15±7.55(P<0.05)。电镜显示新生血管与动脉粥样斑块相邻,新生血管腔内可见淋巴细胞。血管内皮生长因子组CD34阳性细胞数与斑块面积之间呈正相关(r=0.989,P<0.001)。结论血管内皮生长因子165能促进兔动脉粥样硬化斑块的形成与发展。     

动脉粥样硬化狭窄的血管内超声消融疗效

目的:探讨动脉粥样硬化(AS)斑块的血管内超声消融价值。方法:30例冠状动脉AS患者被前瞻性随机分为血管内超声消融组(A组,15例)和单纯PTCA组(B组,15例)。回顾性分析前述两组及9例经血管内超声消融的外周AS患者的疗效。结果:A组经单纯冠脉内超声消融治疗后狭窄程度由(84.1±4.7)％降为(43.0±15.5)％(P<0.05),无1例并发症,但其残余狭窄(43.0±15.5)％仍显著高于B组(P<0.01),B组在PTCA术后残余狭窄为20.9±2.9％。9例外周AS者经单纯血管内超声消融后,平均狭窄程度也由术前的(87.8±7.6)％降为(41.2±9.4)％(P<0.05)。结论:血管内低频高能超声消融术是动脉粥样硬化斑块的一种新的、有效治疗手段。     

结直肠癌患者血清中血管内皮生长因子的水平及其意义

目的:测定结直肠癌患者血清血管内皮生长因子(VEGF)的含量,分析其与临床病理指标间的关系。方法:采用ELISA法测定42例初治结直肠癌患者血清VEGF含量,正常对照30例。结果:结直肠癌患者血清VEGF浓度为274.21±218.38 pg/ml,明显高于正常对照组浓度(169.06±68.01 pg/ml,P<0.02),结肠癌患者血清VEGF浓度为346.52±168.57 pg/ml明显高于直肠癌患者(237.31±124.10 pg/ml,P<0.05)。Dukes B、C、D期组患者血清VEGF浓度与对照组相比均有明显差异(P<0.05),Dukes D期组与Dukes A、B、C期组亦均有明显差异(P<0.05)。结直肠癌患者血清VEGF浓度与年龄、性别无相关性(P>0.05)。结论:VEGF与结直肠癌的发生发展及癌肿部位有关,对探讨结直肠癌的发生机制,病情判断,预后及指导治疗有一定价值,对早期诊断似无帮助。     

维拉帕米对实验兔血管成形术后内膜增殖和血管重塑的影响

目的 :探讨维拉帕米对血管成形术后新生内膜增殖和血管重塑的影响及其机制。方法 :家兔 2 4只 ,随机分为假手术组、对照组和干预组。以球囊导管损伤家兔腹主动脉内膜 ,喂养 4周后 ,对后两组家兔腹主动脉狭窄部位行球囊成形术。其中对照组仅行血管成形术 ,干预组于术前 30min及术后每天给予维拉帕米肌注 [剂量 0 .5mg/ (kg·d) ]。分别于术前 ,术后 4 8h、1周及 4周采静脉血测定 3组家兔血清一氧化氮 (NO)含量。术后 4周处死动物 ,对成形术部位腹主动脉标本作病理形态学检查和免疫组化检查 ,并利用计算机图像分析系统分别测量血管管腔面积、新生内膜面积、内弹力板围绕面积、内膜 /中膜面积 ,计算增殖细胞核抗原 (PCNA)增殖指数(PI)。结果 :血管成形术后血清NO浓度降低 ,但术后 1周和 4周维拉帕米干预组血清NO浓度高于对照组同期水平 ,差异有非常显著性意义 (均 P <0 .0 1)。病理形态学检查示对照组和干预组管腔面积分别为 (6 .4 18±0 .6 5 8)和 (13.4 82± 1.2 0 5 )× 10 4μm2 ;内弹力板围绕面积分别为 (19.719± 1.0 87)和 (2 4 .32 6± 1.4 2 7)× 10 4μm2 。上述指标两组之间比较差异均有非常显著性意义 (均P <0 .0 1)。对照组和干预组新生内膜面积分别为 (13.176± 0 .6 34)和 (10 .195± 0 .5     

养心通脉片对动脉粥样硬化白兔VEGF的表达和新生血管数的影响

目的观察养心通脉片对动脉粥样硬化（AS）白兔血管内皮生长因子（VEGF）的表达和新生血管数的影响和机制.方法利用高脂饲料喂养白兔造模,正常组和模型组用双蒸水灌胃,养心通脉片组用养心通脉液灌胃.1个月后,取出白兔主动脉,运用免疫组化法来观察VEGF和新生血管数.结果模型组和养心通脉片组主动脉斑块都可见棕黄色阳性表达,模型组表达较为强烈,两者比较有统计学意义（P〈0.05）.两组主动脉斑块都可见大于10 μm的颗粒,养心通脉片组颗粒较少,与模型组比较有统计学意义（P〈0.01）.结论养心通脉片在动脉粥样斑块形成后,通过影响VEGF和新生血管的表达来有效地逆转或消退AS斑块.     

消栓通络颗粒对动脉粥样硬化大鼠防治作用及机制研究

目的研究消栓通络颗粒对动脉粥样硬化(AS)模型大鼠的防治作用及其可能的机制。方法采用高脂饲料喂养和腹腔注射维生素D建立AS模型,40只雄性SD大鼠随机分为4组,正常组(喂食基础饲料)、模型组(等量生理盐水)、消栓通络颗粒低高剂量组(1.8 g/kg和7.2 g/kg),12周后处死各组实验大鼠,取主动脉组织,测定超氧化物歧化酶(SOD)、丙二醛(MDA)、内皮素-1(ET-1)、血管内皮生长因子(VEGF)和一氧化氮(NO)水平。结果经消栓通络颗粒治疗后,低剂量组与高剂量组大鼠血管组织中过氧化物代谢产物MDA则明显减少,均有统计学差异(P<0.05;P<0.01),实验大鼠血管组织中SOD略有升高但无统计学差异(P>0.05);消栓通络颗粒高剂量组能够明显降低ET-1水平,升高VEGF水平,与模型对照组比较均具有统计学差异(P<0.05),消栓通络治疗组血管组织样本中NO水平变化,与模型对照组比较无明显差异。结论消栓通络颗粒对AS模型大鼠有一定防治作用,其机制可能与缓解组织氧化应激状态,减轻内皮损伤有关。     

Assessment of plaque vulnerability by angioscopic classification of plaque color

Background

The disruption of yellow plaque and subsequent thrombosis is regarded as the mechanism of acute coronary syndrome. However, there are limited reports on the assessment of plaque vulnerability. Therefore, we tested whether the angioscopically determined yellow color intensity of plaque is associated with the prevalence of thrombosis on the plaque.

Methods

The angioscopic images of 843 patients who underwent catheterization and angioscopic examination from November 1999 to July 2003 for the diagnosis of coronary artery diseases were analyzed. Suspected culprit vessel was observed by angioscopy, and the yellow color intensity (1, light yellow; 2, yellow; 3, intensive yellow) of all yellow plaques (n = 1253) detected in the nonstenotic (diameter stenosis <50%) coronary segments was determined, as well as whether there was thrombosis on the plaques.

Results

The number of detected yellow plaques was 345, 721, and 187 for color grade 1, 2, and 3, respectively. The prevalence of thrombosis detected by angioscopy (15%, 26%, and 52% on the plaque of color grade 1, 2, and 3, respectively, P < .0001) was significantly higher on the plaque of higher yellow color grade.

Conclusions

The yellow color intensity of plaque determined by angioscopy was strongly related with the prevalence of thrombosis on the plaque. The yellow color intensity may be a marker of plaque vulnerability.     

Pathophysiology of plaque rupture and the concept of plaque stabilization

Atherosclerotic coronary artery disease is the major cause of death, in men and women, in the United States and in much of the Western world. Atherosclerosis is responsible for coronary heart disease, limb ischemia, and most strokes. Although luminal narrowing by an atherosclerotic plaque and exaggerated or anomalous vasoconstriction contribute to some of the clinical manifestations of atherosclerotic arterial disease, it is the superim-position of a thrombus over an underlying ruptured or eroded plaque that results in the acute coronary syndromes (unstable angina, acute myocardial infarction, and sudden death) that are the most serious clinical manifestations of this disease.     

冠状动脉血栓形成的病理生理学——斑块破裂和斑块糜烂的作用

本文综述了冠状动脉粥样硬化血栓形成的病理生理学 ,斑块破裂和斑块糜烂在冠状动脉血栓形成中的作用 ,斑块破裂的机制和稳定斑块的治疗原则     

Atherosclerotic plaque biomarkers: beyond the horizon of the vulnerable plaque

Cardiovascular disease (CVD) is the number one cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic inflammatory disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability, leading to thrombus formation and cardiovascular events. Due to the burden of cardiovascular disease, identification of patients at risk for cardiovascular events and treatment stratification is needed. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Imaging modalities have focused on the characteristics of the vulnerable plaque. However, it has become evident that not all so-called vulnerable plaques lead to rupture and subsequent thrombosis. The latter obviously limits the positive predictive value for imaging assessment of plaques and patients at risk. Serum biomarkers have also been studied extensively, but have very limited application in a clinical setting for risk stratification. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future cardiovascular events, also in other territories of the vascular tree. Results look promising and plaque markers can be used to develop imaging modalities to identify patients at risk, or to monitor treatment effect. Plaque biomarker studies do not challenge the definition of the vulnerable plaque, but use its concept in favor of prediction improvement for vascular patients.     

Imaging of high-risk plaque

'High-risk' or 'vulnerable' plaques in the coronary arteries have characteristics that make them more prone to disruption and subsequent thrombosis -- the mechanisms of most acute coronary syndromes (ACS). There are a number of imaging modalities that are capable of visualizing these features. This article discusses invasive modalities for identifying 'high-risk' plaque such as intravascular ultrasound, coronary angioscopy, optical coherence tomography, near-infrared spectroscopy and coronary thermography. It also discusses the use of noninvasive modalities such as computed tomography MRI and ultrasound. When these imaging modalities are combined with standard cardiac risk factors and more novel markers of systemic inflammation and thrombogenicity we can improve our ability to identify the 'high-risk' patient.