摘要
背景
急性冠脉综合征是由于各种原因使冠脉内稳定或不稳定斑块发生破裂，基底胶原纤维暴露，血小板和各种炎性细胞集聚而继发引起血栓形成，导致管腔完全或不完全闭塞所致的一组急症。急性冠脉事件与硬化斑块破裂和血栓形成密切相关，各种炎症因子参与整个过程，炎症可能是一个重要的触发机制，因此在急性冠脉综合征早期抗炎、抗血小板及抗栓治疗极为重要。
前列腺素E_1是一种二十烷类的化合物，其主要有①可直接作用于血管平滑肌，扩张动脉、静脉血管，减低外周血管阻力，减轻心脏的前后负荷；②抑制血小板黏附及聚集，改善血液流变学；③缺血—再灌注损伤保护作用；④增加心肌收缩力，改善冠状动脉循环和保护心肌，增加心肌供血、供氧；⑤抑制儿茶酚胺的释放，保护心肌细胞膜，稳定溶酶体膜；⑥清除循环免疫复合物，减轻对心肌的损害；⑦抑制动脉硬化形成等药理作用。
国外有人发现前列腺素E1能有效抑制急性冠脉综合征患者血小板的黏附聚集，并能改善其血浆纤溶系统，也能抑制外周血管硬化性疾病的炎症活动。但前列腺素E1对急性冠脉综合征患者血浆凝血系统和包括CRP、IL-6、TNF在内的炎症因子国内尚未见有关报道。本研究在急性冠脉综合征介入治疗围术期使用脂质体携载前列腺素E_1，旨在探讨其对急性冠脉综合征患者血浆凝血系统和相应炎症因子的影响。
浙江大学硕士学位论文
方法
2.1研究对象
2002年1月1日至2003年12月31日在邵逸夫医院诊断为急性冠脉综合征
的住院患者。入选标准如下:
(1)年龄)18岁，蕊80岁。
(2)符合急性冠脉综合征诊断标准:
1)不稳定心绞痛末次胸痛发生与就诊前24小时内;
2)急性心肌梗死至少符合下列两项标准:
a.持续胸痛>20分钟;
b.有两个相关导联或以上ST段抬高()0.05mV)，或出现新的左束支
传导阻滞;
c.心肌酶谱升高;
d.超声心动图出现新的节段性室壁运动异常。
(3)冠脉造影证实有一支或一支以上冠状动脉狭窄全70%。
2.2临床资料收集
(1)入选患者的一般情况、冠心病危险因素、相关的实验室指标。
(2)确诊的37例急性冠脉综合征患者介入治疗围术期，常规使用阿司匹
林、抵克力得、肝素和他汀类、硝酸脂类药物及ACEI类药物、乃一受
体阻滞剂等药物使用基础上，在经皮冠状动脉介入术后当天起静脉给
脂质体携载前列腺素EI 20pg，2次/日，连续3天。同期另34例急性
冠脉综合征患者为对照组，在冠脉介入术前、术后均不用脂质体携载
前列腺素E，。
(3)两组患者于术前，术后第3天及出院前共3次测定PT、INR、K盯T及
血小板，术前和术后第3天测定CRP、IL一6及TNF。
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浙江大学硕士学位论文
2.3检测方法及试剂批号
血小板由STKS血常规仪检测。
PT、INR、KPTT由STA一Compact全自动凝血仪采用磁珠法测定，试剂为STA
公司产品，批号:031302。
CRP由Beckman公司Array 360全自动生化分析仪采用速率散射比浊法定量
测定，试剂为Beekman公司产品，试剂批号:465315。
工L一6及TNF采用EI 1 Sa法测定，试剂为Bender公司产品，IL一6试剂批号:
7470018;TNF试剂批号:6025011。
2.4统计学分析
统计分析采用SPSS 1 0.0统计软件包。计量资料以均数士标准差表示，结果进
行t检验，.P<0 .05为统计学存在显著性差异。
结果
1.术后第3天两组PT、工NR、KPTT均有延长，但观察组的PT、INR、KPTT
延长更明显，与对照组相比有显著差异(观察组/对照组叮23.2士1.55/
13.1土1.25:KPTT 38.4士3.65/30.8士4.05，P<0.05);
2.两组术前、出院前所测的PT、INR、KPTT均无明显变化;
3.两组血小板计数任何时候均无明显变化;
4.两组CRP、TNF均有明显升高[观察组(22.32士17.15 mg·L一，/169.33
士32.74 pg·ml一，;对照组21.67士18.23 mg·L一，/157.95士33.42
pg·ml一，，P<0.05)，IL一6升高不明显(观察组1.18士0.27 pg·ml一，;
对照组1.21士0.36 pg .ml一，);
5.3天后观察组CRP、TNF明显下降(10.87士7.54 mg·L一，/76.58士22.51
pg·ml一，)，IL一6无明显变化(1. 29士0.43 pg·ml一，)，而对照组CRP、
IL一6、TNF均无明显变化(1 8.42士1 1.26 mg·L一，/1.13士0.12
pg·ml一’/143.67士36.21 pg·ml一，)。
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浙江大学硕士学位论文
6.两组急性心肌梗死血浆C即、TNF水平较不稳定型心绞痛患者高且有显
著差异(观察组CRP:40.54士20.23/14.82士7.36 mg/L，P(0.01:TNF:
222.36士52.47/145.42士29.25 Pg/ml，P<0.05:对照组CRP:39，52士
22.67/13.59士9.83 mg/L，P(0.01;INF:228.61士48.91/129.57士25.32
p岁ml，P<0.05)。工L一6变化不明显。3天后观察组急性心肌梗死患者血
浆CRP、TNF明显下降有显著差异(CRP:40.54士20.23/14.42士7.48 mg/L，
P(0.05;TNF:222.36士52.47/89.47士27.63 Pg/ml，P<0.05)。对照组变
化不明显
Background:
Acute coronary syndrome (ACS) is one kind of acute syndromes, ranging from unstable angina pectoris to acute myocardial infarction. Its pathological process is characterized by rupture of a stable or unstable atherosclerotic plaque, base collagen fibers exposure, thrombus due to assemblage of plates and several kinds of inflammatory cytokines such as C-reactive proteins (CRP), interleukin-6 (IL-6) or tumour necrosis factor (TNF). As the acute and sub-acute thrombus is the most serious complication in the early stage of percutaneous transluminal coronary angioplasty and stenting, the therapy of anti-plate and anti-thrombus is very important role in the pre-operation of interventional therapy of acute coronary syndrome.
The main effects of Prostaglandin El are 1. Effect on the vascular smooth muscle directly, to expand the artery and vein, to lower the peripheral vascular resistance, to lessen the preload and after loading of heart, 2. To inhibit the adhesion and aggregation of platelets, so as to improve the hemodynamics, 3. to protective effect in reperfusion injury,
4. To increase the myocardial contractile force as well as improve
coronary artery circulation and protect myocardium, it also increase the blood and oxygen supply, 5. To inhibit the release of catecholamine, to protect myocardial cells' membrane, to stable liposomal membrane, 6. To clean up circulating immune complex, to decrease the injury of myocardium, 7. To inhibit the arteriosclerosis forming and so on. So it has pharmacological actions widely.
This article is to aim directly on the effects of liposomal prostaglandin E, in the peri-percutaneous coronary interventional (PCI) of ACS, and observe the effects on the patients' plasma coagulation system and inflammatory cytokines.
Method:
2. 1 Eligible criteria as following:
(1) Age 18 years old, but 80 years old,
(2) Working diagnosis of acute coronary syndromes:
1) Unstable angina episode within the preceding 24 hours,
2) AMI with at least 2 of following criteria:
a. Persistent chest pain >20 minutes,
b. ST elevation in at least 2 corresponding leads ( 0. 05mV), or with new onset of complete left bundle block,
c. Elevation of cardiac enzymes or markers,
d. New regional wall motion abnormality on echocardiography. 2. 2 Thirty-seven consecutive patients who diagnosed as ACS (coronary
artery angiography showed one or more coronary artery stenosis 70%) underwent PCI were included. Lipo-PGEl was given at a dosage of 20Hg, two times a day by intravenously after PCI for three days. Aspirin, ticlid (or Plavix), heparin (or low molecular weight heparin) and statins, 6-blocker as well as ACEI were used at same time in usually dosage. PT, INR, KPTT, platelets and CRP, IL-6, TNF was monitored before PCI and on
the third day. PT, INR, KPTT, platelets was also retest when the patients were discharged. Another thirty-four ACS cases were as placebo group without any Lipo-PGEl using. PT, INR, KPTT, platelets and CRP, IL-6, TNF was tested on the same time.
2. 3 Rate nephelometry with Beckman systems was used to measure the plasma levels of CRP of two groups. And Elisa (Enzyme-linked immunoadsordent assay) method was used to test the levels of IL-6 and TNF. PT, INR, KPTT and platelets were measured by routine method.
2.4 The results of two groups were compared by t test.
Result:
3. 1 PT and KPTT on the third day were prolonged in both groups. But it' s much more longer in Lipo-PGE, group, and it' s also prolonged significantly than control group (Lipo-PGEi group/control group: PT 23. 2 1.5/13. 1 1.2s; KPTT 38. 4 3. 6/30. 8 4. 0s, P<0. 05), and platelet count did not change any more in two groups of all times.
3.2 CRP, TNF were elevated in both two group in early stage of ACS. But IL-6 did not change obviously. On the third day, CRP, TNF decreased significantly in Lipo-PGEl group (from 22.32 17.15 mg-L'Vl69.33 32. 74 pg-ml'1 to 10.87 7. 54 mg-L'V76.58卤22.51 pg-ml-1, P<0. 05), and it did not decrease any more in control group.
3. 3 Subgroup analys
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