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白藜芦醇对高胆固醇血症大鼠血小板活化的影响:CD40-CD40L 系统作为潜在靶点。

Effect of resveratrol on platelet activation in hypercholesterolemic rats: CD40-CD40L system as a potential target.

机构信息

Department of Biochemistry, Faculty of Medicine, Bozok University, 66200 Yozgat, Turkey.

出版信息

Appl Physiol Nutr Metab. 2011 Jun;36(3):323-30. doi: 10.1139/h11-022. Epub 2011 May 16.

DOI:10.1139/h11-022
PMID:21574786
Abstract

Our aim was to investigate whether trans-resveratrol (t-resveratrol), a red wine constituent known for its cardioprotective effects, was able to influence CD40 ligand (CD40L) and its receptor CD40 in platelets of hypercholesterolemic rats. Sixty Wistar rats were divided into 5 groups: control (C), ethanol (E), t-resveratrol (R), hypercholesterolemia (HC), and hypercholesterolemia plus t-resveratrol (HCR). Rats in the C, E, and R groups were fed a normal diet for 80 days. For 20 days before sacrifice, we intraperitoneally (i.p.) administered 0.1 mL ethanol (50% v/v) to the E group, and 0.1 mL t-resveratrol (20 mg·kg(-1)·day(-1)) to the R group. Rats in the HC and HCR groups were fed a 5% cholesterol diet for 80 days. Rats in the HCR group were administered i.p. 0.1 mL t-resveratrol (20 mg·kg(-1)·day(-1)) for 20 days before sacrifice. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), very low-density lipoprotein (VLDL-C), and total triglycerides (TG) were assayed with a commercial colorimetric kit. Platelet P-selectin, CD40, and CD40L expression was determined by flow cytometry. sCD40L and IL6 levels were measured by ELISA. In the HC group, we observed a significant increase in serum TC, LDL-C, VLDL-C, TG, sCD40, and IL-6 levels and platelet activation markers compared with levels in the control group. However, t-resveratrol administration to the HC group (HCR group) attenuated the increase in lipids, sCD40, and IL-6 and down-regulated platelet P-selectin, CD40, and CD40L expressions. A positive correlation was found for serum lipids and all the platelet activation markers. Our study showed that the CD40-CD40L dyad is up-regulated in the presence of hypercholesterolemia and that t-resveratrol administration down-regulated the increase.

摘要

我们的目的是研究白藜芦醇(t-resveratrol)是否能够影响高脂血症大鼠血小板中的 CD40 配体(CD40L)及其受体 CD40。将 60 只 Wistar 大鼠分为 5 组:对照组(C)、乙醇组(E)、t-resveratrol 组(R)、高脂血症组(HC)和高脂血症加 t-resveratrol 组(HCR)。C、E 和 R 组的大鼠喂食正常饮食 80 天。在处死前 20 天,我们向 E 组大鼠腹腔内注射 0.1mL 乙醇(50%v/v),向 R 组大鼠注射 0.1mL t-resveratrol(20mg·kg(-1)·day(-1))。HC 和 HCR 组的大鼠喂食 5%胆固醇饮食 80 天。在处死前 20 天,HCR 组大鼠腹腔内注射 0.1mL t-resveratrol(20mg·kg(-1)·day(-1))。用商业比色试剂盒测定血清总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、极低密度脂蛋白(VLDL-C)和总甘油三酯(TG)水平。用流式细胞术测定血小板 P-选择素、CD40 和 CD40L 的表达。用 ELISA 测定 sCD40L 和 IL6 水平。在 HC 组,与对照组相比,我们观察到血清 TC、LDL-C、VLDL-C、TG、sCD40 和 IL-6 水平以及血小板活化标志物显著增加。然而,t-resveratrol 给药到 HC 组(HCR 组)减轻了血脂、sCD40 和 IL-6 的增加,并下调了血小板 P-选择素、CD40 和 CD40L 的表达。血清脂质与所有血小板活化标志物呈正相关。我们的研究表明,CD40-CD40L 二聚体在高脂血症时上调,而 t-resveratrol 给药可下调其增加。

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