银杏黄酮苷元干预兔颈总动脉损伤后内膜增生及血凝素样氧化低密度脂蛋白受体1的表达

Effect of ginkgo flavone aglycone intervention on intimal proliferation and lectin-like oxidized low-density lipoprotein receptor-1 expression in rabbits following carotid balloon injury

背景:银杏叶提取物中的黄酮苷元具有较强的抗氧化活性,课题组前期实验证实可抑制氧化低密度脂蛋白诱导内皮细胞表达血凝素样氧化低密度脂蛋白受体1。目的:进一步探讨银杏黄酮苷元对兔颈总动脉内皮损伤后内膜增生和血凝素样氧化低密度脂蛋白受体1表达的影响。方法:将雄性新西兰大白兔随机分为对照组、假手术组、模型组和治疗组。对照组予普通饲料,其余各组予高脂饮食,假手术组仅作颈外动脉结扎,模型组和治疗组均球囊损伤右颈总动脉,治疗组损伤后用银杏黄酮苷元灌胃。4周后检测各组血脂水平,观察各组右颈总动脉形态,用免疫组织化学法和RT-PCR检测血凝素样氧化低密度脂蛋白受体1蛋白和mRNA表达。结果与结论:模型组术后4周内膜增生明显,有粥样斑块形成,血凝素样氧化低密度脂蛋白受体1表达明显增加(P<0.05)。治疗组银杏黄酮苷元灌胃4周后内膜增生较轻,内膜面积,血凝素样氧化低密度脂蛋白受体1阳性细胞数和其基因表达水平均低于模型组(P<0.05),但血脂与模型组比较无差异。提示银杏黄酮苷元可减轻新生内膜增生及动脉粥样硬化病粥样斑块的形成,这种作用可能与抑制兔颈总动脉内皮损伤后血凝素样氧化低密度脂蛋白受体1的表达有关。

BACKGROUND： Flavone aglycone, a component of ginkgo biloba extract, has strong antioxidant activity. Preliminary studies have demonstrated that ginkgo flavone aglycone （GFA） can inhibit lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） expression induced by oxidized low density lipoprotein. OBJECTIVE： To investigate the effect of GFA on the intimal proliferation and LOX-1 expression in rabbits after carotid endothelial injury. METHODS： New Zealand male rabbits were randomly divided into the control, sham surgery, model, and treatment groups. All rabbits were fed with high cholesterol chow except that in the control group. Rabbits in the sham surgery group underwent surgery without endothelium injury, those in the model and treatment groups underwent carotid balloon injury. GFA was administered daily to the treatment group by gavages. Serum lipids in 4 groups were detected at 4 weeks after operation. The carotid artery segments were harvested for histomorphometry observation. LOX-1 levels were measured though SP immunohistochemistry assay and RT-PCR. RESULTS AND CONCLUSION： Neointimal proliferation and atherosclerosis was found in carotid artery of the model group at 4 weeks after operation, and the expression of LOX-1 was notably increased （P〈0.05）. In the treatment group, the intimal area, intimal/medial area ratio and the LOX-1 expression were smaller than those of the model group （P〈0.01）, but the serum lipids levels had no difference. GFA can inhibit neointimal proliferation and atherosclerosis progress, which may be related to down-regulated expression of LOX-1 after carotid balloon injury.