急性心肌梗死患者血清胎盘生长因子的动态变化及意义
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摘要
目的:胎盘生长因子( placental growth factor, PLGF/PlGF)是血管内皮生长因子(vascular endothelial growth factor,VEGF)家族中的一员。研究显示它可以刺激血管平滑肌细胞生长,促进巨嗜细胞的趋化性聚集,并诱导其产生组织因子如肿瘤坏死因子和单核细胞趋化性蛋白-1,促发炎症反应,可作为动脉粥样硬化不稳定炎症斑块的一个主要助长因素。同时,C-反应蛋白作为一种炎症因子亦是动脉粥样硬化不稳定炎症斑块的一个助长因素。因此,对胎盘生长因子及超敏C-反应蛋白的进一步研究将有助于提高对动脉粥样硬化发生发展的认识,为动脉粥样硬化的防治提供一个新的思路。本实验主要研究急性心肌梗死(acute myocardial infarction,AMI)患者血清胎盘生长因子水平及超敏C-反应蛋白(high-sensitivity C-reactive protein,Hs-CRP)的动态变化及其与心肌梗死面积大小、心室重构程度的关系。
     方法:AMI组患者60例,男33例,女27例,年龄37-82岁,平均(56.4±8.0)岁。并将所收AMI患者分为溶栓再通组与非溶栓组,其中溶栓再通组男性29例,女性6例,平均年龄(52.8±7.2)岁,非溶栓组男性18例,女性7例,平均年龄(51.8±9.1)岁。正常健康人30例,其中男性12例,女性18例,年龄为31-62岁,平均(52.1±6.6)岁。所有的研究对象除外体重指数(BMI)≥25kg/m2和<18.5kg/m2患者,除外脑血管病、全身大动脉疾病、肝肾疾病及代谢性疾病(糖尿病、甲状腺功能亢进)及炎症患者。各组研究对象在年龄、性别、BMI方面,差异无统计学意义。所有AMI研究对象于起病第12小时、第3天、第7天时采集肘静脉血5ml,对照组采集空腹肘静脉血5ml,胎盘生长因子采用酶联免疫吸附测定法(ELISA)测定;Hs-CRP采用免疫透射比浊法测定;并测定AMI 14天时超声心动图,了解左心室射血分数(left ventricular ejection, LVEF),左心室舒张末期容积(left ventricular end-diastolic volume, LVEDV),观察PlGF与LVEF及LVEDV的相关性;观察AMI组与对照组血清PlGF、Hs-CRP指标的变化;溶栓再通组与非溶栓组各指标间的变化;各指标之间的相关性;以及各指标与血清心肌酶谱相关性,及其对心室重构的影响。
     结果:AMI患者发病12小时、第3天、第7天血清PlGF分别为(17.47±4.85)pg/mL、(20.47±5.42)pg/mL、(9.30±2.89)pg/mL,除第7天组外均明显高于健康对照组(7.56±1.37)pg/mL(P<0.01);其中第3天显著高于第7天,第7天与对照组相比差异无统计学意义;而同时测定的Hs-CRP分别为(33.57±32.18)mg/L、(41.76±10.19)mg/L、(28.03±8.34 )mg/L亦明显高于健康对照组(1.5±2.0)mg/L(P<0.01)。血清PlGF与血清CK-MB峰值呈正相关(r=0.131;P>0.05);Hs-CRP与血清CK-MB峰值呈正相关(r=0.364;P<0.01);同一时间点的PlGF与Hs-CRP呈正相关(r=0.014;P>0.05)。血清PlGF与LVEF呈显著负相关(r=-0.654;P<0.01),与LVEDV呈显著正相关(r=0.845;P<0.01)。
     结论:1 AMI患者第12小时、第3天、第7天血清PlGF、Hs-CRP水平显著高于健康人群,其中第3天最高,提示PlGF和Hs-CRP可能参与AMI的病理发展过程;2溶栓再通组PlGF与Hs-CRP显著低于非溶栓组,提示PlGF和Hs-CRP的水平受再灌注影响;3血清PlGF与Hs-CRP呈正相关,PlGF与心肌梗死标志物CK-MB呈正相关,Hs-CRP与CK-MB呈正相关,提示PlGF和心肌损伤面积有关。4血清PlGF与LVEF呈显著负相关,与LVEDV呈显著正相关,提示PlGF水平可能影响左心室重构。
Objective: Placental growth factor ( PlGF ) is a member of the vascular endothelial growth factor (VEGF)family of growth factors. PlGF stimulates vascular smooth muscle cell growth, recruits macrophages into atherosclerotic lesions, up-regulates production of tumor necrosis factor and monocyte chemotactic protein -1 by macrophages, stimulates the inflammtory reaction. It plays a fundamental role for unstable inflammation plaque of atherosclerosis.Simultaneously,CRP also plays a fundamental role for unstable inflammation plaque of atherosclerosis as a inflammation factor. Thus, furture research of PlGF and Hs-CRP will elevate the recogniaion of early and advanced atherosclerotic lesions. Furthermore, we will investigate the role of PlGF on the development of acute myocardial infarction (AMI).
     Methods: 60 patients with acute myocardial infarction (AMI), who came from the inpatients of 2th hospital affiliated with the HEBEI Medical University ( 33 males and 27 females ), with average age of (56.4±8.0) years. The patients with AMI were divided into two groups : the thrombolysis group ( 29 males and 6 females ) with average age of (52.8±7.2) years and the non-thrombolysis group ( 18 males and 7 females ) with average age of (51.8±9.1) years. 30 healthy staffs were recruited as normal control group. All subjects not only had excluded body mass index ( BMI )≥25kg/m2 and <18.5kg/m2, but also had no other diseases such as Cerebrovascular disease, Main Artery disease, Liver and Kidney disease, Metabolic disease ( Diabetes, Hyperthyreosis ). The age, sex , BMI showed no difference among three groups. Taking ulnar venous blood 5ml on an empty stomach, infusing anticoagulation tube, using centrifugal machine, 3000 r /min, centrifuging 10min, the plasma in Eppendorf was preserved in -80℃refrigerator. Serum placental growth factor (PlGF) were detected by enzyme-linked immuneosorbent assay (ELISA), while the levels of Hs-CRP were detected by immunity transmission turbidity. Cardiac ultrasonography were detected on 14 days of onset, the relationship between adiponectin and the markers of Serum placental growth factor, Hs-CRP was analyzed.
     Results: The level of Serum placental growth factor at 12hours and the 3days and 7 days were respectively (17.47±4.85) pg/mL, (20.47±5.42) pg/mL, (9.30±2.89) pg/mL, significantly raised than control group (7.56±1.37) pg/mL (P<0.01) except the 7 days group, the level of Serum Hs-CRP at the same time were respectively (33.57±32.18) mg/L, (41.76±10.19) mg/L, (28.03±8.34)mg/L, significantly raised than control group (1.5±2.0) mg/L(P<0.05). The level of placental growth factor was positively correlated with that of CK-MB (r=0.131;P>0.05) and Hs-CRP was positively correlated with that of CK-MB (r=0.364;P<0.01), while placental growth factor was positively with Hs-CRP ( r=0.014;P>0.05). The level of placental growth factor was negatively correlated with left ventricular ejection (LVEF) (r=-0.654;P<0.01), and positive correlation with left ventricular end-diastolic volume(LVEDV) (r= 0.845; P<0.01).
     Conclusion: 1 The level of serum PlGF and Hs-CRP at 12hours and the 3days and 7 days were significantly raised than control group,and the 3 days were the highest,suggested that PlGF and Hs-CRP contribute to the pathophysiological process of aute myocardial infarction; 2 The level of serum PlGF and Hs-CRP of the thrombolysis group were significantly raised than that of the nonthrombolysis group,suggested that the level of serum PlGF and Hs-CRP were affected by reperfusion ; 3 The level of serum PlGF was positively correlated with that of CK-MB ,and the level of Hs-CRP was positively correlated with that of CK-MB while PlGF was positively with Hs-CRP , suggested that PlGF related to myocardial injury area; 4 The level of PlGF was negatively correlated with LVEF, and positive correlation with LVEDV,suggested that PlGF may influence left ventricular remodeling.
引文
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