Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes

This study was to explore the effect and mechanism of Probucol on STZ-induced erectile dysfunction in diabetic rats. Thirty SD male rats aged 12 weeks were given intraperitoneal injection of STZ after fasting for 12 hr. Diabetic rats were haphazardly partitioned under two assemblies and administered 0 or 500 mg/kg probucol by oral gavage to 12 weeks. Control group was intraperitoneally injected with physiological saline, and saline was administered by oral gavage daily. Intracorporeal pressure was used to evaluate erectile function. Levels of proteins were detected using immunohistochemistry and Western blotting. α-SMA and vWF were detected using immunofluorescence staining. After treatment, erectile function in probucol group was significantly improved. Endoplasmic reticulum stress-related proteins were expressed higher in DM group than in sham group, while expression of these proteins decreased significantly in probucol group. However, α-SMA and vWF were expressed at lower levels in DM group than in sham group, and probucol treatment reversed this phenomenon. Finally, Bax and Caspase3 were expressed at higher levels and Bcl-2 was expressed at lower levels in DM group, while the opposite result was obtained in probucol group. In conclusions, probucol improves erectile function by reducing endothelial dysfunction and inhibiting PERK/ATF4/CHOP pathway in STZ-induced diabetic rats.     

普鲁布考等药物对溶血磷脂酰胆碱引起的牛脑基底动脉条收缩的影响

目的 :研究溶血磷脂酰胆碱 (L PC)对牛脑基底动脉条收缩的影响及普罗布考等药物的保护作用。方法 :通过描记基底动脉条的张力变化 ,测定 L PC对基底动脉条收缩的影响。结果 :L PC能剂量依赖性 (1× 10 - 9～ 1× 10 - 5 mol/ L )促进基底动脉条收缩 ,在 1× 10 - 5 mol/ L时 ,收缩达最大 ,为 (15 1.0± 18.4) %。当用 Triton X- 10 0 (0 .1% )破坏血管内皮层后 ,L PC诱导的血管收缩作用消失。银杏叶提取物 (EGb)、普罗布考 (Pro)和维生素 E(Vit E)能剂量依赖性地减弱 L PC诱导的牛脑基底动脉条收缩。 结论 :药物 EGb,Pro和 Vit E能拮抗 L PC诱导的牛脑基底动脉条收缩。     

Succinobucol: review of the metabolic,antiplatelet and cardiovascular effects

Background: Succinobucol (AGI-1067) was developed as a probucol derivative with anti-inflammatory and antioxidant properties. It has undergone Phase III clinical trials to determine its place in the treatment of atherosclerotic disease. Objective: This paper reviews the available history, pharmacology and preclinical and clinical trial data of succinobucol. Methods: Data were compiled following review of publications indexed in Medline and International Pharmaceutical Abstracts, industry media releases and relevant bibliographies. Results/conclusion: In preclinical studies, succinobucol exhibited antioxidant, anti-inflammatory, antihyperglycemic and antiplatelet properties; however, these effects have not resulted in a reduction in cardiovascular clinical end points in clinical trials. Although proposed antihyperglycemic effects are being investigated, safety concerns and lack of clear cardiovascular benefit may limit its clinical use as an antihyperglycemic agent.     

Endothelial dysfunction in streptozotocin-diabetic rats is not reversed by dietary probucol or simvastatin supplementation

Summary Oxidative stress and dyslipidaemia are key features of diabetes mellitus and may be involved in mediating the vascular endothelial dysfunction associated with this disease. The aim of this study was to examine the effect of dietary lipid-lowering and antioxidant agents on vascular endothelial function and oxidative stress. Diabetic male Sprague-Dawley rats (i. v. streptozotocin, 45 mg/kg) were fed for 4 weeks on a standard diet or on a diet supplemented with either the lipid-lowering antioxidant probucol (1 % w/w in diet) or the 3-hydroxy 3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor simvastatin (0.01 % w/w in diet). Responses to noradrenaline, acetylcholine, and sodium nitroprusside were assessed in small mesenteric arteries (mean internal diameter 300 ± 5 μm, n = 80) mounted on a small vessel myograph. Plasma concentrations of total cholesterol and triglycerides were significantly raised in standard-fed diabetic rats and significantly reduced in probucol and simvastatin-fed diabetic rats. 8-epi-prostaglandin (PG)F₂α, an indicator of oxidative stress, was raised in liver and aorta from diabetic rats compared to controls. Probucol supplementation reduced 8-epi-PGF₂α in aorta and liver of diabetic rats but increased 8-epi-PGF₂α content in plasma and aorta from control animals. The abnormal relaxation to acetylcholine in arteries from the diabetic rats (pEC₅₀ diabetic 6.763 ± 0.172 vs control 7.541 ± 0.175; p < 0.05) was not improved by probucol or simvastatin. These data, therefore, do not support a role for oxidative stress or dyslipidaemia in mediating the impaired ACh-induced endothelium-dependent relaxation of small mesenteric arteries from the streptozotocin-diabetic rat. [Diabetologia (1998) 41: 157–164] Received: 4 August 1997 and in revised form: 29 September 1997     

瑞舒伐他汀剂量加倍和联合普罗布考治疗冠心病合并高胆固醇血症患者的疗效比较

目的比较瑞舒伐他汀剂量加倍与联用普罗布考对冠心病合并高胆固醇血症患者的疗效。方法在2012年1月至2013年12月在长海医院心内科就诊的冠心病患者中,选取经瑞舒伐他汀10mg、每晚1次治疗3个月以上,低密度脂蛋白胆固醇(LDL-C)仍不能达标者,将其随机分为他汀剂量加倍组(瑞舒伐他汀片20mg、每晚1次)和联合治疗组(瑞舒伐他汀片10mg、每晚1次+普罗布考片250mg、每天2次),每组各34例,治疗3个月。比较两组患者治疗前和治疗后外周血脂水平的变化以及不良反应发生率。结果治疗前两组患者一般情况、血脂水平差异无统计学意义(P>0.05)。治疗后3个月,两组患者总胆固醇(TC)、LDL-C均明显下降(P<0.05);联合治疗组三酰甘油(TG)明显下降(P<0.05);他汀加倍组、联合治疗组高密度脂蛋白胆固醇(HDL-C)分别显示升高和下降的趋势,但均未达到统计学差异(P>0.05)。与他汀加倍组相比,联合治疗组TC、LDL-C降得更低(P<0.05),LDL-C达标率更高(P<0.05),但HDL-C明显降低(P<0.05)。两组患者不良反应发生率比较,联合治疗组明显低于他汀加倍组(P<0.05)。结论对于冠心病合并高胆固醇血症患者,瑞舒伐他汀与普罗布考联合使用优于瑞舒伐他汀剂量加倍的疗效,且具有更高的安全性。     

普罗布考对糖基化终末产物引发心脏微血管内皮功能紊乱的作用

目的:观察普罗布考（probucol）对糖基化终末产物（AGEs）作用后的心脏微血管内皮细胞iNOS表达的影响。方法: 原代培养心脏微血管内皮细胞,AGEs（100 mg/L）体外模拟高糖环境,在probucol(5 μmol/L,10 μmol/L,20 μmol/L) 作用后,检测ROS、NO和iNOS变化情况。结果: 与AGEs组比较,probucol组中ROS蛋白表达降低,NO生成增加,而 iNOS蛋白表达降低,且显示有浓度依赖性。结论: probucol可能通过对抗氧化应激的途径,缓解AGEs引发的心脏微血管内皮功能障碍。     

普罗布考对老年下肢动脉硬化症患者内皮舒张功能的影响

目的　评价普罗布考对老年下肢动脉硬化症患者内皮舒张功能的影响。方法　采用随机、单盲、自身对照和组间对照方法 ,将 5 4例老年下肢动脉硬化症患者分为两组 ,其中普罗布考治疗组 33例 ,服用普罗布考 0 .5g,2次 /d ,同时服用阿司匹林 10 0mg ,1次 d ;常规治疗组 2 1例 ,仅服用阿司匹林 10 0mg,1次 d ,疗程均为 12周。采用高分辨率超声技术 ,对治疗前后血管内皮舒张功能进行检测。结果　 (1)治疗前老年下肢动脉硬化症患者肱动脉血流介导的舒张功能 (FMD)和硝酸甘油介导的舒张功能 (NMD)均明显低于健康人群 ;(2 )治疗后 ,普罗布考治疗组总胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL C)及高密度脂蛋白胆固醇 (HDL C)明显降低 ;(3)治疗后 ,普罗布考治疗组FMD明显增加 ,而NMD无显著性改变。结论　 (1)老年下肢动脉硬化症患者内皮依赖的舒张功能降低 ;(2 )普罗布考能够改善老年下肢动脉硬化症患者内皮功能 ,并具有良好的调脂作用 ;(3)普罗布考引起的HDL降低并不影响其改善内皮功能的作用。     

普罗布考联合阿托伐他汀疗法对急性脑梗死患者高敏C反应蛋白的影响

[背景]探讨普罗布考联合阿托伐他汀对急性脑梗死患者静脉血高敏C反应蛋白含量的影响.[病例报告]选取60例急性脑梗死患者,随机分为2个组,即普罗布考联合阿托伐他汀组(实验组)和阿托伐他汀组(对照组),每组各为30例,观察用药前后患者静脉血C反应蛋白含量的变化情况.用药30d后,两组患者静脉血高敏C反应蛋白含量较用药前均显著下降,实验组降低更为明显,与对照组比较有显著性差异.[讨论]普罗布考联合阿托伐他汀可减轻急性脑梗死患者的炎症反应.     

普罗布考和科素亚对血管成形术后生长因子表达的影响

目的 :研究普罗布考和科素亚对血管成形术后再狭窄的预防作用和对生长因子表达的影响。方法 :新西兰白兔30只均予高脂饮食 ,1周后进行髂动脉球囊拉伤术 ,随机分为对照组 (C组 )、普罗布考组 (P组 )、科素亚组 (L组 )。术后第 4周进行血管形态学检查 ,用免疫组化方法检测胰岛素样生长因子 - 1受体 (IGF- 1 R)、血管内皮生长因子(VEGF)、增殖细胞核抗原 (PCNA)表达。结果 :与 C组相比 ,P组和 L 组血管腔面积明显扩大 (P<0 .0 1 ) ,IGF- 1 R、VEGF和 PCNA表达明显减少 (P<0 .0 1 ) ,P组和 L组相比无显著性差异 (P>0 .0 5 )。结论 :普罗布考和科素亚可以显著减轻兔髂动脉血管成形术后再狭窄的形成 ,抑制 IGF- 1、VEGF和 PCNA的表达 ,而两药之间则无显著性差异     

丙丁酚抑制体外氧化低密度脂蛋白诱导的单核细胞对内皮细胞的粘附

目的:研究丙丁酚抑制体外氧化低密度脂蛋白诱导的单核细胞对内皮细胞的粘附机制.方法:采用酶联免疫法检测丙丁酚对内皮细胞粘附分子、细胞间粘附分子1(ICAM-1)、血管细胞粘附分子1 (VCAM-1)、P-选择素和E-选择素表达的影响,对比分析丙丁酚和上述粘附分子单克隆抗体抑制氧化低密度脂蛋白诱导的单核细胞对内皮细胞的粘附作用.结果:丙丁酚呈浓度依赖性抑制氧化低密度脂蛋白诱导的单核细胞对内皮细胞的粘附,丙丁酚浓度从10μmol/L增加到80μmol/L,单核细胞对内皮细胞的粘附从16.7％降低至7.0％(P<0.01),同时ICAM-1和P-选择素表达分别被抑制75％和72％(P相似文献