【作者】 何德化；

【导师】 李卫华；

【作者基本信息】 福建医科大学 ， 内科学， 2008， 硕士

【摘要】 研究背景冠心病是威胁人类健康的主要疾病之一,在有些国家,由冠状动脉粥样硬化引起的心脏病(冠心病)已成为人群中首位的死亡原因。目前冠心病的发病机制尚未完全阐明,近年的研究表明,炎症是冠心病发生发展过程中的核心因素。通过检测血清中炎性因子的水平,能够间接反映冠心病的病变程度以及斑块的易损性。作为炎症因子之一,分泌型磷脂酶A2(sPLA2)为脂蛋白相关性磷脂酶A2的亚型之一,主要由血管壁平滑肌细胞与巨噬细胞等产生,属于钙依赖的磷脂酶家族,主要位于巨噬细胞集聚区、脂质核心区以及病变内膜的细胞外基质内。目前认为,sPLA2与动脉粥样硬化的发生发展相关,可能机制是水解细胞膜及脂蛋白的磷脂酰胆碱,并产生致炎症反应及动脉粥样硬化的溶血磷脂胆碱(LysoPC)和氧化脂肪酸(OxFA)[1]。Hs-CRP在冠心病发病中的作用已日益受到重视,其价值明显高于传统的冠心病危险因素生化指标,其血清水平同临床心血管病有浓度依赖关系,可以作为预测冠心病事件的独立因子[2、3]。目的本研究以冠脉造影正常者为对照组,研究各组冠心病患者血清中sPLA2、hs-CRP水平的变化特点,冠状动脉粥样硬化斑块性质与血清中sPLA2、hs-CRP水平的相关性以及介入治疗对血清中sPLA2、hs-CRP水平的影响,探讨sPLA2、hs-CRP在冠心病发病机制中的作用,以及检测血清中sPLA2、hs-CRP水平在冠心病诊疗中的价值。方法冠心病患者104例,男66例,女38例,其中稳定型心绞痛(SA)28例、不稳定型心绞痛(UA)54例、急性心肌梗塞(AMI)22例。所有患者均行冠状动脉造影术。冠状动脉造影显示至少一支主要冠状动脉存在病变,部分单支病变患者在行经皮冠脉介入治疗(PCI)前进行IVUS检查。另外选择冠状动脉造影正常者20例为对照组。所有患者均在采血前禁食10小时以上,并于次日清晨空腹采血5ml;所有患者均分别于术前即刻、术后即刻、术后6小时、术后24小时采血5ml,采用双抗体夹心酶联免疫吸附法(ELISA)测定血清中sPLA2的浓度,并采用乳胶增强免疫比浊法测定血清中hs-CRP的浓度。所有数据资料用SPSS11.5软件包行统计学处理。P<0.05为差异有统计学意义,P<0.01为差异有显著统计学意义。结果1. AMI组、UA组、SA组和NS组血清sPLA2、hs-CRP水平两两比较,差异均有显著统计学意义(P﹤0.01)。设定以sPLA2大于50.00pg/ml为阳性判断标准,各组阳性率分别为100%、90%、55%和5%。2.冠脉造影正常对照组术前术后血清sPLA2、hs-CRP水平无明显变化(P﹥0.05)。PCI患者,术后血清sPLA2、hs-CRP水平较术前明显升高,差异有统计学意义(P﹤0.01)(AMI组术后即刻血清hs-CRP水平较术前即刻比较,P﹤0.05)。3.软斑块组血清sPLA2、hs-CRP水平与纤维斑块组、钙化斑块组比较,差异有显著统计学意义(P﹤0.01);纤维斑块血清sPLA2水平与钙化斑块组比较,差异有显著统计学意义(P﹤0.01),血清hs-CRP水平与钙化斑块组比较,差异有统计学意义(P﹤0.05)。向心性斑块组血清sPLA2水平与偏心性斑块组比较,差异有显著统计学意义(P﹤0.01);hs-CRP水平与偏心性斑块组比较,差别有统计学意义(P﹤0.05)。结论1. sPLA2、hs-CRP参与了冠心病的发生发展,可作为冠脉病变程度及病情变化的预测因子,辅助冠心病的诊疗。2.PCI造成冠状动脉内膜损伤或斑块破裂,短期内触发或加重了冠状动脉局部炎症反应。sPLA2、hs-CRP参与了冠状动脉局部炎症。血清sPLA2、hs-CRP水平可能间接反映冠状动脉局部炎症程度。3.血清sPLA2、hs-CRP水平有可能间接反应斑块的性质及其偏心程度,判断斑块的易损性。更多还原

【Abstract】 Background:Coronary artery disease (CAD) is one of the principal diseases that threaten human health so much that it’s the primar cause of death in some countries. At present, the pathogenesy of CAD is not fully studied. Current studies have shown that inflammation plays an essential role in the development and procedure of CAD. The extent of pathological changes and vulnerability of plaque can be determined indirectly by serum inflammatory factor level.As one of the inflammation factors,secretory type II phosphatidolipase A2, a subtype of lipoprotein-related phosphatidolipase A2, is mainly produced by smooth muscle cells and macrophages and belongs to calcium-depended phosphatidolipase family, which locates mainly in macrophages gathering place, lipid core area and extracellular matrix of pathological intima. Currently, it’s thought to be related with the development of atherosclerosis by possibly hydrolyzing cellular membrane and phosphatidylcholine in lipoprotein to produce proinflammatory reaction and atherosclerotic lysophosphatidylcholine (LysoPC) and oxidized fatty acid (OxFA) [1]. Increasing evidence has shown that hs-CRP plays an important role in the development of CAD which is considered as An independent prediction factor because its serum concentrated-depende- nt relationship with cardiovascular events[2,3].Objective:This study aimed to study the character of serum level changes of sPLA2 and hs-CRP in every group patients with CAD, the dependability between atherosclerotic plaque features and serum levels of sPLA2 and hs-CRP, and the influence of intervention therapy on serum levels of sPLA2 and hs-CRP. To explore the role of sPLA2 and hs-CRP in CAD pathogenesy and the value of serum level of sPLA2 and hs-CRP in CAD diagnosis and theropy.Methods:One hundred and four patients (male 66, female 38) with CAD were enrolled in this study including stable angina (SA) 28, unstable angina (UA) 54 and acute myocardium infarction (22). All patients underwent coronary angiography with pathological changes in at least one coronary artery. Intravascular ultrasound (IVUS) was performed before percutaneous coronary intervention (PCI) in partly patients. In addition, 20 patients with normal CAG served as control.5 ml of blood was taken from all patients without food over 10 h before blood taken. Blood was taken before and 0, 6, 24h after intervention, respectively. Serum sPLA2 level was measured by double antibody enzyme linked immunoysorbent assay (ELISA) and hs-CRP by emulsion reinforced immunoturbidimetry (ITM). All results were statistically analyzed with SPSS 11.5. P<0.05 was considered statistic difference , P<0.01 was considered significantly statistic difference.Results:1. Compared with each other, serum levels of sPLA2 and hs-CRP are statistically different in AMI, UA, SA and NS groups (p<0.01).The positive standard of sPLA2 is considered as 50pg/ml, positive ratio is 100%, 90%, 55% and 5% in AMI, UA , SA and NS group.2. Serum levels of sPLA2 and hs-CRP didn’t change much before and after intervention in NS group while in the patients with PCI the serum levels of sPLA2 and hs-CRP increased significantly after intervention (p<0.01) (in AMI group, p<0.05 compared with those before imtervention).3. Serum levels of sPLA2 and hs-CRP were statistically higher in soft plaque group compared with fibrous plaque group and calcified plaque group (p<0.01). In fibrous plaque group, serum levels of sPLA2 and hs-CRP were significantly higher than those in calcified plaque group, p<0.01 and p<0.05, respectively. The same as that, in afferens plaque group and eccentricity plaque group.Conclusions:1. sPLA2 and hs-CRP play important roles in the development of CAD and can be considered as a predict factor in the diagnosis of CAD.2. PCI results in intima damage in coronary artery and plaque rupture and triggers or aggravates local inflammation reaction. sPLA2 and hs-CRP took part in local inflammation in coronary artery .The serum level of sPLA2 and hs-CRP may indirectly reflect local inflammation in coronary artery.3. Serum levels of sPLA2 and hs-CRP could reflect plaque characters such as eccentricity and vulnerability.更多还原