白藜芦醇对高脂血症大鼠血小板聚集的影响及其机制研究

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (7): 769-773.

白藜芦醇对高脂血症大鼠血小板聚集的影响及其机制研究

白云霞

杭州市第一人民医院,杭州 310000,浙江

收稿日期:2012-11-19 修回日期:2013-05-25 出版日期:2013-07-26 发布日期:2013-06-20
作者简介:白云霞,女,主管药师,研究方向:临床药理学。Tel: 0571-86453876 E-mail: byx1211@126.com

Study of the effects and the mechanism of resveratrol on platelet aggregation in hyperlipidemia rats

BAI Yun-xia

Hangzhou First Hospital, Hangzhou 310000,Zhejiang,China

Received:2012-11-19 Revised:2013-05-25 Online:2013-07-26 Published:2013-06-20

摘要/Abstract

摘要： 目的: 研究白藜芦醇对高脂血症大鼠血小板聚集的影响及其可能机制。方法: 建立大鼠的高脂血症模型,同时连续 i.g. 给予白藜芦醇(50 mg·kg^-1·d^-1)或空白溶媒 30 d,测定大鼠血浆TC 、 TG 、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)、NO、内皮一氧化氮合酶(eNOS)、P-选择蛋白、血栓烷B₂(TXB₂)和6-酮-前列腺素F_1α(6-Keto -PGF_1α),ADP诱导的血小板5 min最大聚集率。结果: 与高脂模型组比较,高脂饲料白藜芦醇组大鼠在连续 i.g. 给予白藜芦醇(50 mg·kg^-1·d^-1)30 d 后,大鼠血浆TG、TC、LDL-C含量均下降,分别下降19%、31%、51%,HDL-C含量增加 1.33 倍;SOD和eNOS活力升高,NO和6-Keto -PGF_1α含量增加,MDA、P-选择蛋白、TXB₂含量降低,ADP诱导的血小板 5 min 最大聚集率降低。结论: 白藜芦醇能有效降低血小板聚集,可能是通过降低血脂水平,防止脂质过氧化和保护内皮细胞完整,影响NO合成,维持血浆或组织中的TXA₂和PGI₂平衡及细胞内外的钙离子平衡等多环节来发挥作用。

关键词: 白藜芦醇, 高脂血症, 血小板聚集

Abstract: AIM: To explore the effects and the mechanism of resveratrol on platelet aggregation in hyperlipidemia rats.METHODS: Experimental hyperlipidemia rats were ig administrated of resveratrol (50 mg·kg^-1·d^-1) or vehicle for 30 d. The levels of TC, TG, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), superoxide dismutase (SOD), NO, endothelial nitric oxide synthase (eNOS), granulemembrane protein-140(GMP-140),thromboxaneB₂ (TXB₂),6-keto -prostaglandin F_1α (6-keto-PGF_1α) and platelet maximal aggregation rate(MAR)which was induced by ADP in 5 minute were measured.RESULTS: Compared with the high fat diet (HFD) group, the levels of TG, TC,LDL-C were decreased respectively by 19%, 31%,51% and the level of HDL-C increased in 1.33 folds after the rats fed and ig resveratrol (50 mg·kg^-1·d^-1) for 30 d. The activities of SOD and eNOS and the content of NO and 6-keto-PGF_1α in resveratrol group were increased (P<0.01).And the contents of MDA, GMP-140,TXB₂ and MAR in resveratrol group were decreased (P<0.05).CONCLUSION: Platelet aggregation rate was decreased in experimental hyperlipidemia rats by i.g. administration of resveratrol, its mechanism closely correlates with decline of plasma lipid and with anti- peroxide of lipid , protecting vaso endothelial cells , improving the synthesis of NO , keeping the balance of TXA₂ and PGI₂ in tissue or plasma and the balance between extracellular calcium and intracellular calcium.

Key words: Resveratrol, Hyperlipidemia, Platelet aggregation

中图分类号:

R363.2

白云霞. 白藜芦醇对高脂血症大鼠血小板聚集的影响及其机制研究[J]. 中国临床药理学与治疗学, 2013, 18(7): 769-773.

BAI Yun-xia. Study of the effects and the mechanism of resveratrol on platelet aggregation in hyperlipidemia rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 769-773.

参考文献

[1] Pervaiz S, Holme AL. resveratrol: its biologic targets and functional activity[J]. Antioxid Redox Signal, 2009, 11(11):2851-2897.
[2] 杨雨民,王世君,王宏强,等.白摹芦醇体外抗血小板作用及机制初探[J].中国药学杂志,2009,44(3):191-194.
[3] Pellegrini N, Simonetti P.Composition of platelet phospholipids aftemorderate consumption of resveratrol in healthy volunteers[J].Eur J Cli Nutr,1996,50(8):535-541.
[4] 杨迎暴,朴英杰. 白藜芦醇对急性脊髓损伤早期脂质过氧化反应和活性氧水平的抑制作用[J]. 中国临床药理学与治疗学,2002,7(3):193-196.
[5] Natella F,Ghiselli A,Guidi A,et al. resveratrol mitigates the postprandial increase of LDL susceptibility to oxidation[J]. Free Radical Bio Med, 2001,30(9):1036-1044.
[6] Nascimento NR, Lessa LM, Kerntopf MR, et al. Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide[J]. Proc Natl Acad Sci USA, 2006, 103(1): 218- 223.
[7] Wallerath T, Li H, Gödtel-Ambrust U,et al. A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase[J].Nitric Oxide,2005,12(12):97-104.
[8] Pedreño J, Hurt-Camejo E, Wiklund O, et al. Platelet function in patients with familial hypertriglyceridemia: evidence that platelet reactivity is modulated by apolipoprotein E content of very-low-density lipoprotein particles[J].Metabolism, 2000, 49(7): 942-949.
[9] Andrew DB,Gregory YH.Hyperthesis:Is soluble P-selectin a new marker of platelet activation[J]?Atherosclerosis,1997,128(2):135-138.
[10] Nesbitt WS, Giuliano S, Kulkarni S, et al1 Intercellular calcium communication regulates platelet aggregation and thrombus growth[J]. Cell Biol, 2003, 160(7): 11512-11611.

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