Effects of cilostazol on lipid and fatty acid metabolism

Abstract Cilostazol is a selective inhibitor of phosphodiesterase III with anti-platelet-aggregatory and vasodilating properties. Randomised, double-blind, placebo-controlled trials in 2702 patients with intermittent claudication demonstrated that cilostazol significantly increased walking distances compared with placebo. Furthermore, the agent has beneficial effects on the serum lipid profile and fatty acid composition in plasma. Consequently, cilostazol may be useful to prevent atherosclerosis from progressing by ameliorating lipid and fatty acid metabolism.     

西洛他唑治疗糖尿病合并下肢动脉闭塞症的功效及安全性观察

目的：观察西洛他唑治疗糖尿病合并下肢动脉闭塞症的效果及安全性。方法：选择糖尿病合并下肢动脉闭塞症患者33例,给予西洛他唑第一周50mg,2次／日。第二周始改为100mg,2次／日,观察并检测治疗前后症状体征,双下肢血管直径及峰值血流速度,肝肾功能,血尿常规,血脂及血液流变学等指标。结果：患者主观症状改善率在80％以上,双下肢血流峰值速度治疗后有显著性增加（P＜0．01）,血尿常规,肝肾功能等各项指标治疗前后无明显差异。结论：西洛他唑对糖尿病合并下肢动脉闭塞症是一种安全有效的药物。     

西洛他唑降低链脲佐菌素诱发糖尿病大鼠肾脏VCAM-1表达

目的　探讨西洛他唑对高糖大鼠肾组织VCAM - 1的影响及对肾脏的可能保护作用。方法　雄性SD大鼠,链脲佐菌素(STZ)制备糖尿病大鼠模型。观察西洛他唑12周后对血糖、糖化血红蛋白、肾重/体重比值、肾脏VCAM - 1mRNA及蛋白表达的影响。结果　糖尿病对照组及各治疗组肾重/体重比值均明显增加(P <0 . 0 1);VCAM - 1mRNA表达在糖尿病组明显升高,药物治疗后有显著改善( P <0. 0 1);Westernblot各组均有VCAM - 1表达,糖尿病组较正常组表达增强,药物治疗后呈下降趋势。结论　STZ诱发的糖尿病大鼠肾脏VCAM - 1表达增加,西洛他唑降可低糖尿病大鼠肾组织VCAM - 1mRNA和蛋白表达,对糖尿病肾脏具有保护作用。     

Effect of cilostazol on arteriovenous fistula in hemodialysis patients

BackgroundThe maturation and patency of permanent vascular access are critical in patients requiring hemodialysis. Although numerus trials have been attempted to achieve permanently patent vascular access, little have been noticeable. Cilostazol, a phosphodiesterase-3 inhibitor, has been shown to be effective in peripheral arterial disease including vascular injury-induced intimal hyperplasia. We therefore aimed to determine the effect of cilostazol on the patency and maturation of permanent vascular access.MethodsThis single-center, retrospective study included 194 patients who underwent arteriovenous fistula surgery to compare vascular complications between the cilostazol (n = 107) and control (n = 87) groups.ResultsThe rate of vascular complications was lower in the cilostazol group than in the control group (36.4% vs. 51.7%; p = 0.033), including maturation failure (2.8% vs. 11.5%; p = 0.016). The rate of reoperation due to vascular injury after hemodialysis initiation following fistula maturation was also significantly lower in the cilostazol group than in the control group (7.5% vs. 28.7%; p < 0.001). However, there were no significant differences in the requirement for percutaneous transluminal angioplasty (PTA), rate of PTA, and the interval from arteriovenous fistula surgery to PTA between the cilostazol and control groups.ConclusionCilostazol might be beneficial for the maturation of permanent vascular access in patients requiring hemodialysis.     

糖尿病大鼠坐骨神经病变与细胞黏附分子-1和P-选择素变化的相关性及西洛他唑的治疗作用

目的　研究糖尿病 (DM )大鼠黏附分子CD5 4、CD6 2p变化及其与坐骨神经病变的关系 ,探讨西洛他唑对糖尿病神经病变 (DPN)和黏附分子的影响。　方法　将实验大鼠分为正常组 (8只 )、糖尿病组 (8只 )、胰岛素组 (7只 )和西洛他唑组 (7只 )。测定各组坐骨神经传导速度和血浆单个核细胞CD5 4、血小板CD6 2p含量 ,观察坐骨神经超微结构变化。　结果　西洛他唑治疗组与DM组相比 :(1)坐骨神经传导速度明显加快 ;DM组 =(2 0 .3± 2 .2 )m/s ,西洛他唑组 =(2 8.9± 7.9)m /s ,q =3 .50 ,P <0 .0 5。 (2 )血浆单个核细胞表面CD5 4水平明显降低 ;DM组 =(65± 15) % ,西洛他唑组 =(2 5± 9) % ,q =7.50 ,P <0 .0 5。 (3 )西洛他唑有降低血小板表面CD6 2p的趋势 ,与DM组相比无显著差异。 (4)坐骨神经超微结构的病理变化明显改善。　结论　DM大鼠CD5 4、CD6 2p表达增加与DPN有明显的相关性 ,西洛他唑可降低其表达并改善糖尿病神经病变     

Phosphodiesterase-3 inhibitor （cilostazol） attenuates oxidative stress-induced mitochondrial dysfunction in the heart

Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.     

臂踝脉波传播速度的诊断价值及西洛他唑的干预效果

2型糖尿病组臂踝脉波传播速度(baPWV)均比正常患者组高,糖尿病合并高血压组baPWV比糖尿病正常血压组高,baPWV与年龄、收缩压和舒张压有关。西洛他唑干预后baPWV明显下降。     

The role of cilostazol in the treatment of intermittent claudication

SUMMARY

This paper represents a review, by experts, of current opinion and information on intermittent claudication (IC) and the role that cilostazol plays in its treatment. IC is a common and debilitating condition that has a significant adverse impact on health-related quality of life (HR-QoL). It is currently under-recognised as a powerful marker of increased cardiovascular (CV) risk. The clinical priority is secondary prevention – sometimes referred to as best medical therapy aimed at reducing CV risk. However, the priority for most patients (often overlooked by clinicians) is symptom relief: an increase in walking distance leading to an improvement in HR-QoL. The symptoms of IC may be improved by exercise, pharmacotherapy, and when these are unsuitable or unsuccessful, endovascular or surgical intervention.     

献血者服用西洛他唑后的延期献血

目的 探讨服用西洛他唑后献血者的筛选以及延期献血期限的设定.方法 根据两洛他唑的药理学和药动学性质以及血小板的生理学性质确定其安全献血期限.结果 服用过西洛他唑的献血者应该延期献血,期限为7 d.结论 服用过抗血小板药物的献血者延期献血有利于保证临床用血的质量.