葡萄籽原花青素对心血管的保护作用

近几年来国外对葡萄籽原花青素的研究发现有心血管保护作用.它的自由基清除能力可抗心肌缺血再灌注损伤;通过抑制低密度脂蛋白的氧化作用而抗动脉粥样硬化,并具有降低血压、调节血脂等心血管方面的疾病.     

葡萄籽原花青素对心血管的保护作用

近几年来国外对葡萄籽原花青素的研究发现有心血管保护作用。它的自由基清除能力可抗心肌缺血再灌注损伤；通过抑制低密度脂蛋白的氧化作用而抗动脉粥样硬化，并具有降低血压、调节血脂等心血管方面的疾病。     

葡萄籽原花青素药理研究进展

综述近几年来国外对葡萄籽原花青素在抗氧化、抗心肌缺血再灌注损伤、抗动脉粥样硬化、降低血压、多器官保护以及抗癌等方面药理作用及机制的研究进展.     

原花青素提取物对糖尿病大鼠氧化应激的影响

目的观察葡萄籽原花青素提取物(GSPE)对糖尿病(DM)大鼠体内氧化应激水平的影响。方法给W istar大鼠腹腔注射链脲佐菌素(STZ)60 mg/kg,制成模型,随机分为DM模型对照组、氨基胍组(150 mg.kg-1.d-1)和GSPE低、中、高三个剂量组(50、150、450 mg.kg-1.d-1),并作正常对照。常规喂养12 w后取大鼠血清用比色法比较各组超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果与DM模型对照组比较,GSPE可以显著升高血清SOD、降低MDA。结论GSPE能够降低DM大鼠的氧化应激水平,具有防治DM慢性并发症的作用。     

原花青素联合维生素E对动脉粥样硬化大鼠血脂及抗氧化的影响

目的探讨葡萄籽原花青素(GSP)与维生素(V) E联合作用对动脉粥样硬化(AS)大鼠血脂及抗氧化的影响。方法选用健康雄性Sprague-Dawley(SD)大鼠60只随机分为空白组和造模组,采用高脂膳食法+腹腔注射VD3建立AS模型。4 w后,将造模组分5组:模型组; GSP+VE低、中、高剂量组和阿托伐他汀组,每组10只,灌胃给药干预4 w。结束后空白组和模型组各随机抽出2只确认建模成功。测定大鼠的血清血脂水平、内皮舒张因子一氧化氮(NO)、血清超氧化物歧化酶(SOD)、丙二醛(MDA)的含量及抗超氧阴离子O2-、抗羟自由基(-OH)的能力。结果与空白组比较,模型组血脂水平均显著升高(P<0. 05),抗氧化能力显著降低(P<0. 05);与模型组相比,GSP+VE低剂量组能改善血清中血脂水平(P<0. 05),而对AS的抗氧化作用不显著。GSP+VE中、高剂量组的血脂水平均依次显著降低(P<0. 05),抗氧化能力显著升高,可以显著改善NO浓度(P<0. 05)。结论 GSP联合VE通过降血脂及抗氧化作用以延缓AS的形成。     

苦瓜提取物对糖尿病小鼠的抗氧化作用

目的研究苦瓜提取物对四氧嘧啶(ALX)糖尿病小鼠的抗氧化作用及其机制。方法采用腹腔注射ALX构建糖尿病小鼠模型,造模成功后,分为模型对照组,苦瓜提取物低、中、高3个剂量(20、40、80 mg/kg)组,另设正常对照组。连续灌胃给药(ig)28 d,以小鼠血清和肝脏组织的超氧化物歧化酶(SOD)活力、糖化血红蛋白(HbA1c)水平、丙二醛(MDA)水平为测定指标,研究不同剂量苦瓜提取物对糖尿病小鼠的抗氧化作用。结果苦瓜提取物能显著提高糖尿病小鼠血清和肝脏组织的SOD活力,降低血清HbA1c水平,降低血清和肝脏组织的MDA水平。结论苦瓜提取物具有较强的抗氧化作用,其机制可能与其清除体内自由基,修复自由基引发的细胞膜破损等作用有关。     

葡萄籽原花青素耐缺氧作用的实验研究

目的观察葡萄籽原花青素(GSP)的耐缺氧作用.方法采用小鼠常压耐缺氧实验和小鼠断头实验,观察GSP对缺氧小鼠存活时间、耗氧量及断头后张口喘气时间的影响.结果 GSP能明显延长常压缺氧小鼠的存活时间及脑缺氧小鼠张口喘气时间,降低耗氧量.结论 GSP具有耐缺氧作用,其作用机制可能与增加大脑供血和降低心脑耗氧有关.     

葡萄籽原花青素预防兔实验性动脉粥样硬化研究

葡萄籽原花青素 (grapeseedproanthocyanidin ,GSP)是从葡萄籽中提取的一类多酚化合物 ,最重要的组成单元是黄烷 3 醇 ,大多数为 ( ) 儿茶素和 (- ) 表儿茶素。近年研究证实 ,GSP有极强的抗氧化活性 ,且毒副作用极低。本研究探讨了GSP抗动脉粥样硬化作用及其机制。1.材料与方法 :(1)实验分组 :2 4只雄性新西兰兔 ,随机分为 3组 ,每组 8只 :正常对照组饲喂标准颗粒饲料 ;模型组饲喂含 1%胆固醇的颗粒饲料 ;干预组饲喂含 1%GSP和 1%胆固醇的颗粒饲料。饲料量为每只每天 10 0g。 (2 )检测方法 :实验前及实验的第 4、8、12周末分别采取…     

葡萄籽原花青素对兔实验性动脉粥样硬化的干预研究

目的 探讨葡萄籽原花青素（GSP）对免实验性动脉粥样硬化（AS）的预防作用及其机制。方法 雄性新西兰免24只，随机分为3组，每组8只：正常对照组饲喂标准颗粒饲料；模型组饲喂含1％胆固醇的颗粒饲料；干预组饲喂含1％GSP和1％胆固醇的颗粒饲料。分别于实验前及实验的第4、8、12周末空腹经耳中动脉采血，测血清总胆固醇（Tc）、低密度脂蛋白胆固醇（LDL-C）以及血浆氧化低密度脂蛋白（OX-LDL），并在12W末处死动物，留取主动脉和心脏作形态学检查。结果 与模型组相比，干预组的血清TC、LDL-C无明显变化（P〉0．05），但其血浆OX-LDL的水平明显下降（P〈0．05或0．01）。干预组主动脉弓斑块面积占总面积的百分比明显低于模型组（P〈0．01）；心脏上1／3处横切片显示心壁内冠状动脉大、中分支的狭窄程度，干预组明显轻于模型组（P〈0．01）；透射电镜观察显示干预组主动脉和心肌的超微结构病变明显轻于模型组。结论 GSP能有效地抑制AS斑块的形成和发展，该作用的发挥与其能够抑制血浆LDL的氧化有关。     

葡萄籽原花青素对实验性动脉粥样硬化兔基质金属蛋白酶和氧化低密度脂蛋白的影响

目的观察葡萄籽原花青素(GSPE)对实验性动脉粥样硬化兔基质金属蛋白酶2,9(MMP-2,9)和氧化低密度脂蛋白(ox-LDL)的影响,探讨其抗动脉粥样硬化的可能机制。方法雄性新西兰兔24只,随机分为3组:正常对照组,饲喂标准颗粒饲料;模型组,饲喂含1%胆固醇的颗粒饲料;干预组,饲喂含1%GSPE和1%胆固醇的颗粒饲料。于实验前及实验的第4,8,12周末空腹经耳中动脉采空腹血,检测血清MMP-2,9和血浆ox-LDL水平。于12周末,留取主动脉作常规病理观察和免疫组化染色。结果与模型组相比,GSPE干预组病变明显减轻,免疫组化染色显示主动脉MMP-2和MMP-9表达明显减少,血清MMP-2,MMP-9和ox-LDL水平明显下降。结论GSPE有明显的抗动脉粥样硬化效应,该效应与其抗氧化、抑制MMP有关。     

葡萄籽原花青素与阿托伐他汀联合应用治疗动脉粥样硬化的研究

目的 观察葡萄籽原花青素(GSPE)及阿托伐他汀对新西兰兔动脉粥样硬化基质金属蛋白酶-9(MMP-9)的影响,探讨其抗动脉粥样硬化的可能机制. 方法 将雄性新西兰兔30只随机分为5组,对照组饲喂标准颗粒饲料,共24周.其余各组均饲喂含1%胆固醇的颗粒饲料,12周后模型组饲喂含1%标准颗粒饲料,GSPE组饲喂含1%GSPE的颗粒饲料,阿托伐他汀组饲喂含阿托伐他汀(2.5 mg·kg~(-1)·d~(-1))的颗粒饲料,GSPE联用阿托伐他汀(联合组)饲喂含阿托伐他汀(2.5 mg·kg~(-1)·d~(-1))和1%GSPE的颗粒饲料,共12周.24周末处死全部新西兰兔,留取主动脉作常规病理观察和免疫组化染色.于实验前及实验的第12、24周末经耳中动脉采空腹血,检测血清MMP-9水平. 结果 模型组主动脉粥样斑块内和血清MMP-9表达均比对照组增加(均P<0.05).GSPE组、阿托伐他汀组、联合组与模型组比较病变轻,主动脉壁MMP-9表达减少,血清MMP-9水平下降,分别为(1.06±0.21)、(1.07±0.20)、(0.81±0.16)与(1.32±0.24)ng/ml,均P<0.05.结论 GSPE及阿托伐他汀均具有抗动脉粥样硬化效应,该效应的发挥与其抑制MMP有关,二者联合应用作用更明显.     

葡萄籽原花青素联合阿托伐他汀治疗老年颈动脉粥样硬化患者的观察

目的 观察葡萄籽原花青素和阿托伐他汀联合应用对老年患者颈动脉粥样硬化的疗效. 方法 将存在颈动脉粥样硬化斑块的老年高脂血症患者122例,随机分为单药组63例,给予阿托伐他汀20 mg/d;联合用药组59例,给予阿托伐他汀l0mg/d和葡萄多酚胶囊400mg/d.治疗前及治疗后3、6、12个月测定患者平均最大颈动脉内中膜厚度(MMCIMT)、斑块积分、斑块性质及血脂和超敏C反应蛋白(hs-CRP)水平的变化. 结果 治疗3个月后,单药组和联合用药组患者与治疗前比较血清总胆固醇(TC)[(4.9±1.0)比(6.5±0.7)mmol/L、(4.7±0.6)比(6.3±0.6)mmol/L]、三酰甘油(TG)[(2.3±0.5)比(2.9±0.4)mmol/L、(2.2±0.7)比(3.0±0.4) mmol/L]、低密度脂蛋白胆固醇(LDL-C) [(3.3±0.9)比(4.2±0.7)mmol/L、(3.1±0.6)比(4.0±0.6)mmol/L]降低(均P＜0.01),且随着治疗时间的延长进一步降低.联合用药组患者治疗3个月后高密度脂蛋白胆固醇(H DL-C)水平较治疗前升高20.2％ (P＜0.05).治疗后两组患者血清hs-CRP水平均下降(均P＜0.05).单药组治疗3个月MMCIMT较治疗前减小1.3％(P＞0.05),治疗6个月减小3.4％ (P＞0.05),12个月减小5.1％(P＜0.05).联合用药组治疗3个月后MMCIMT较治疗前减小2.0％(P＞0.05),6个月减小5.3％(P＜0.05),12个月减小8.6％(P＜0.01).12个月组间比较差异有统计学意义(P＜0.01).单药组治疗3个月斑块积分较治疗前减小6.8％(P＞0.05),治疗6个月减小14.5％ (P＞0.05),12个月减小19.2％(P＜0.05);联合用药组患者治疗3个月斑块积分减少13.1％(P＞0.05),且随着治疗时间的延长,斑块积分进一步降低(6个月下降28.0％,P＜0.05;12个月下降45.0％,P＜0.01).治疗6个月(P＜0.05),两组12个月联合治疗组斑块积分降低更明显(P＜0.01);联合用药组较单药组斑块总数和不稳定斑块数减少更明显. 结论 葡萄籽原花青素与阿托伐他汀联合应用,可加强抗动脉粥样硬化治疗的效果.     

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques

Background Atherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract (GSPE) has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use. Methods Consecutive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness (CIMT) were randomly assigned to the GSPE group (n = 146) or control group (n = 141). The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was performed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT (MMCIMT), plaque score, echogenicity of plaques and ischemic vascular events were recorded. Results As anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT progression (4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months) and plaque score (10.9% decrease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months) for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also decreased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack (TIA), arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower (P = 0.02, 0.08, 0.002, respectively) compared with the control group. Conclusions GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.     

Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis

Oxygen-derived free radicals mediate tissue damage in acute and chronic pancreatitis. Low levels of natural antioxidants in pancreatitis indicate their increased utilization as scavengers of free radicals. Combination therapy with selenium, beta-carotene, methionine, and vitamins C and E are known to improve symptoms of chronic and recurrent pancreatitis. This, however, requires many tablets to be taken daily, which is impractical and may reduce compliance. Three patients with chronic pancreatitis (two with a history of alcohol excess and one idiopathic) are reported. Treatment with narcotic analgesics and pancreatic enzyme supplements had failed to control their symptoms. The addition of a commercially available IH636 grape seed proanthocyanidin extract (commercially known as ActiVin) to their treatment regimen led to a reduction in the frequency and intensity of abdominal pain as well as resolution of vomiting in 1 patient.     

葡萄籽原花青素对AGEs诱导的内皮细胞分泌NO及ET-1的影响

目的观察葡萄籽原花青素（GSP）对糖基化终产物（AGEs）诱导的人脐静脉内皮细胞（HUVEC）一氧化氮（NO）、内皮素（ET-1）生成及其mRNA表达的影响。方法牛血清白蛋白（BSA）与葡萄糖在体外共同孵育以制备糖基化终产物（AGE-BSA），将培养的HUVEC与不同浓度的GSP（5、15、25μg/ml）预孵育4h，再加入200μg/mlAGE-BSA共同培养，分别用硝酸还原酶法及放免法测定培养上清液中NO及ET-1的含量，用逆转录PCR（RT-PCR）检测一氧化氮合酶（eNOS）及ET-1 mRNA的表达，用激光共聚焦显微镜检测细胞内活性氧簇（ROS）的产生。结果HUVEC用AGE-BSA刺激后明显增强细胞内ROS产生，并能减少内皮细胞NO的分泌及eNOS mRNA的表达，增加内皮细胞ET-1的分泌及其 mRNA的表达（P〈0.01）。而GSP预孵育则对AGE-BSA诱导的上述作用具有显著的改善作用，并呈剂量依赖性（P〈0.01）。结论GSP可能通过抑制细胞内氧化应激而影响AGEs诱导的内皮细胞NO及ET-1生成，改善血管内皮功能，这对于防治糖尿病慢性血管并发症具有重要的意义。     

Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury.

There is increasing evidence to indicate cardioprotective effects of red wine consumption. Such cardioprotective properties of wine have been attributed to certain polyphenolic constituents of grapes. The purpose of this investigation was to examine whether proanthocyanidins derived from grape seeds possess cardioprotective properties. Rats were randomly divided into two groups: grape-seed proanthocyanidin was administered orally to one group of rats (100 mg/kg/day) for 3 weeks while the other group served as control. After 3 weeks, rats were killed, hearts excised, mounted on the perfusion apparatus and perfused with Krebs-Henseleit bicarbonate (KHB) buffer. After stabilization hearts were perfused in the working mode for baseline measurements of contractile functions. Hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Coronary perfusates were collected to monitor malonaldehyde formation, a presumptive marker for oxidative stress development. At the end of each experiment, the heart was processed for infarct size determination. Peroxyl radical scavenging activity of proanthocyanidin was determined by examining its ability to remove peroxyl radical generated by 2,2'-azobis (2-amidinopropane) dihydrochloride while hydroxyl radical scavenging activity was tested with its ability to reduce 7-OH.-coumarin-3-carboxylic acid. The results of our study demonstrated that proanthocyanidin-fed animals were resistant to myocardial ischemia reperfusion injury as evidenced by improved recovery of post-ischemic contractile functions. The proanthocyanidin-fed group revealed reduced extent of myocardial infarction compared to the control group. Fluorimetric study demonstrated the antioxidant property of proanthocyanidin as judged by its ability to directly scavenge peroxyl radicals. Taken together, the results of this study showed that grape seed-proanthocyanidins possess a cardioprotective effect against ischemia reperfusion injury. Such cardioprotective property, at least in part, may be attributed to its ability to directly scavenge peroxyl and hydroxyl radicals and to reduce oxidative stress developed during ischemia and reperfusion.     

葡萄籽原花青素提取物对膳食诱导肥胖小鼠氧化应激的影响

目的观察强抗氧化剂葡萄籽原花青素提取物（grape seed procyandins extract,GSPE,低聚物〉85％）对肥胖伴氧化应激小鼠抗氧化能力的影响。方法选用C57BL／6J小鼠,观察高、中、低剂量GSPE（400mg/kg·d^-1、200mg／kg·d^-1和100mg／kg·d^-1）对膳食诱导肥胖（diet-induced obesity,DIO）小鼠成模过程中体重、体脂、血清游离脂肪酸、血清肿瘤坏死因子α、肝谷胱甘肽过氧化物酶（GSH-Px）、肝过氧化物歧化酶（SOD）、肝总抗氧化能力（T-AOC）和丙二醛（MDA）的影响。结果GSPE能显著降低DIO小鼠的体重、体脂比,降低血清游离脂肪酸、血清肿瘤坏死因子α的水平,提高肝GSH-Px、SOD、T-AOC活性。结论GSPE有良好的预防DIO小鼠肥胖及其相伴的氧化应激的作用。     

Grape seed proanthocyanidin extract reduces renal ischemia/reperfusion injuries in rats

Activation of reactive oxygen species and inflammation are implicated in renal ischemia/reperfusion (I/R) injuries. This study investigated whether grape seed proanthocyanidin extract (GSPE) protects against renal I/R injury by its effect on reactive oxygen species and the inflammation pathway. Wistar rats were administered GSPE before renal ischemia, followed by reperfusion for 24 hours. Plasma concentrations of urea, creatinine and cystatin C were measured for renal dysfunction. Serum and tissue superoxide dismutase activity and glutathione peroxidase and malondialdehyde levels were measured. Renal sections were analyzed for histological grading of renal injury, and nuclear factor-κB activity was determined. GSPE significantly reduced increases in urea, creatinine and cystatin C; increased kidney superoxide dismutase activity and glutathione peroxidase levels and reduced malondialdehyde levels. GSPE reduced histological renal damage and nuclear factor-κB activity. These results suggest that GSPE reduces renal dysfunction and injury caused by renal I/R.