以西洛他唑为基础的三联抗血小板在冠状动脉支架植入术中的研究进展

经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)已经成为冠状动脉粥样硬化性心脏病的重要手段之一。术后常规的抗血小板治疗尤为重要,阿司匹林联合腺苷二磷酸受体拮抗剂氯吡格雷的双联抗血小板治疗(dual antiplatelet therapy,DAPT)已被广泛应用于接受冠状动脉支架手术的患者中。但即使接受标准的抗血小板治疗,仍有1%~4%患者发生支架内血栓事件,其死亡率高达40%以上。而西洛他唑是新型的活性多样的抗血小板药物,可针对术后的多种危险因素进行干预,对PCI的患者可降低心血管事件和支架内再狭窄(restenosis,RS)的发生。以西洛他唑联合阿司匹林、氯吡格雷的三联抗血小板治疗(triple antiplatelet therapy,TAPT)已被日、韩及我国的很多心脏中心应用于PCI术后抗血小板治疗。为帮助医生在临床应用中更合理的使用西洛他唑,笔者综述TAPT在PCI术后患者中的研究进展。     

Pharmacodynamic interaction study of Allium sativum (garlic) with cilostazol in patients with type II diabetes mellitus

Aim:

Garlic is available as an over-the-counter herbal supplement and is known to have antiplatelet properties. Because of scarcity of clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we tried to evaluate the effects of coadministration of single and multiple doses of garlic and cilostazol on platelet aggregation.

Materials and Methods:

The study was a randomized, open label, placebo-controlled, crossover study of type II diabetic patients, where 14 patients were enrolled and 10 completed the study. The patients were administered 600 mg aged garlic extract, 100 mg cilostazol, 600 mg aged garlic extract, and cilostazol or placebo for seven days as per prior randomization schedule. Blood samples for platelet aggregation and bleeding time and clotting time were collected before and 2, 4, and 6 hours after single-dose drug administration and after seven days of treatment.

Results:

After single- and multiple-dose administration of garlic, there was a significant inhibition of platelet aggregation at 2 hours, whereas with cilostazol, the inhibition was significant at all the three time points tested, with 4 hours showing maximum inhibition. Coadministration of garlic and cilostazol in single and multiple doses for seven days did not produce any significant change in the antiplatelet activity of the individual drugs.

Conclusions:

Coadministration of aged garlic extract and cilostazol did not enhance the antiplatelet activity compared with individual drugs. Large randomized trials are needed to further evaluate the possible interaction of garlic in higher doses and in combination with other antiplatelet activity drugs.     

西洛他唑对人血管内皮细胞增殖及P38MAPK表达的抑制作用

目的 观察西洛他唑(CLZ)对体外培养的血管内皮细胞(VEC)增殖和磷酸化P38丝裂原活化蛋白激酶(MAPK)表达的影响.方法 体外培养人脐静脉血管内皮细胞饵(HUVECs)株EA.hy926,应用10、30、100、300 μmo/L CLZ作用24h(同时设空白对照组)后采用MTT法检测HUVECs的增殖状态,Western blotting检测细胞磷酸化P38MAPK蛋白的表达.结果 与空白对照组比较,30、100、300 μmo/L CLZ组细胞A值降低,且30、100、300μmo/L CLZ组之间比较细胞A值依次降低,差异均有统计学意义(P＜0.05);与空白对照组比较,30、100、300 μmol/L CLZ组细胞磷酸化P38MAPK蛋白的表达下降,且300 μmol/L CLZ组细胞磷酸化P38MAPK蛋白表达低于30μmol/L CLZ组,差异有统计学意义(P＜0.05).结论 CLZ对体外培养的VEC增殖和磷酸化P38MAPK蛋白的表达均有明显的抑制作用.     

西洛他唑对缺血性卒中患者血小板聚集功能影响

目的 探讨西洛他唑常用剂量下,血小板聚集率的变化规律.方法 60例脑梗死患者,每日服用西洛他唑50mg,一天两次,分别于服药前、服药后2周、4周、8周测定血小板最大聚集率及斜率的变化.结果 与服药前相比,西洛他唑用药前和用药后血小板聚集率有显著性下降,而用药后2周、4周、8周比较无明显变化.结论 西洛他唑对缺血性卒中患者血小板聚集有很好的抑制作用.     

瑞舒伐他汀联合西洛他唑治疗老年高脂血症的疗效观察

目的对瑞舒伐他汀联合西洛他唑治疗老年高脂血症的临床疗效进行观察和分析。方法抽取我院确诊的55例老年高脂血症患者,作为研究对象,随机分为对照组和研究组。对照组采用每天一次瑞舒伐他汀10mg,研究组在对照组治疗的基础上,加用50mg西洛他唑,每天2次。12周后,对治疗前后的各项指标进行比较。结果研究组效果明显优于对照组,差异有统计学意义(P<0.05)。不良反应出现5例,但并不严重。结论瑞舒伐他汀联合西洛他唑治疗老年高脂血症,比单药瑞舒伐他汀治疗效果更佳,且不良反应小疗效可靠,适合老年高脂血症患者使用。     

Effect of Cilostazol on Endothelial Cell Denudation and Proliferation in Canine Vein Grafts

The purpose of the present study was to examine the effects of cilostazol on endothelial cell denudation and proliferation in vein grafts used as arterial substitutes. Unilateral aortoiliac bypass was performed using the lateral jugular vein in 20 mongrel dogs. The animals were divided into two groups according to whether or not cilostazol was given. The grafts were removed at intervals of 1 day and 50 days, and the luminal surface was assessed for endothelial cell coverage (%). The denudation of endothelial cells was less extensive in the cilostazol group than in the control group on postoperative day 1. There was significantly more proliferation of endothelial cells in the control group over the course of time than in the cilostazol group. In conclusion, cilostazol significantly prevented early endothelial cell denudation, although it did not appear to stimulate successive endothelial cell proliferation. Therefore, cilostazol may help preserve an intact intima, which would potentially result in the inhibition of intimal hyperplasia. Received: October 6, 2000 / Accepted: May 15, 2001     

Synergistic Efficacy of Concurrent Treatment with Cilostazol and Probucol on the Suppression of Reactive Oxygen Species and Inflammatory Markers in Cultured Human Coronary Artery Endothelial Cells

In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3~3 µM) with probucol (0.03~0.3 µM) significantly suppressed TNF-α-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-α release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3~3 µM) with probucol (0.1~0.3 µM) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.     

抗血小板制剂对家兔血管成形术后基质金属蛋白酶及其抑制剂表达的影响

观察抗血小板制剂西洛他唑对血管成形术后基质金属蛋白酶及组织型金属蛋白酶抑制剂表达的影响.建立家兔二次损伤的血管成形术模型,随机分为对照组、高脂组及西洛他唑组.观察血管成形术后4周腹主动脉内膜增生情况,用免疫组织化学及逆转录聚合酶链反应检测基质金属蛋白酶2和9及组织型金属蛋白酶抑制剂1和2的蛋白及mRNA表达.结果发现,血管成形术4周后,西洛他唑组新生内膜面积减少,管腔面积增大,与高脂组相比差异显著;基质金属蛋白酶2和9及组织型金属蛋白酶抑制剂1和2的蛋白及mRNA表达水平与高脂组相比明显减低.结果提示,抗血小板制剂西洛他唑可以抑制血管成形术后内膜基质金属蛋白酶及组织型金属蛋白酶抑制剂的表达,干预基质代谢,抑制内膜增生.     

西洛他唑对2型糖尿病尿白蛋白排泄率的影响

目的探讨西洛他唑治疗2型糖尿病早期肾病的临床疗效.方法将60例血压正常伴微量白蛋白尿的2型糖尿病患者,随机分为两组：治疗组30例,予口服西洛他唑片（50 mg,bid）;对照组30例,予口服安慰剂维生素B1（10 mg,bid）,两组均治疗3个月.观察患者治疗前后尿白蛋白排泄率（UAER）的变化.结果治疗组与治疗前比较,UAER明显下降（P＜0.01）,下降幅度达51.6%,约3%病人仅有轻微头痛反应.对照组治疗前后UAER无明显变化（均P＞0.05）.结论西洛他唑能显著降低糖尿病尿白蛋白的排泄,对糖尿病早期肾病具有治疗作用,且安全性好.