益肾活血胶囊对同型半胱氨酸致兔动脉粥样硬化MCP1mRNA表达及NFκB活化的影响.DOCVIP

临床医学论文-益肾活血胶囊对同型半胱氨酸致兔动脉粥样硬化MCP1mRNA表达及NFκB活化的影响 【摘要】? 目的 探讨益肾活血胶囊对同型半胱氨酸（Hcy）致兔动脉粥样硬化（AS）单核细胞趋化蛋白1（MCP1）基因表达及核因子κB（NFκB）活化的影响。方法 将40只新西兰兔随机分为正常组、模型组、益肾活血胶囊小剂量组、益肾活血胶囊大剂量组及西药（叶酸、维生素B6、维生素B12）组，除正常组外，其他组建立高Hcy血症及AS动物模型，然后分别给予相应的药物治疗。采用高效液相色谱技术检测血浆Hcy浓度、HE染色观察血管形态学变化、实时定量PCR检测动脉壁MCP1基因表达、Western blot分析核因子κB抑制因子α（IκBα）蛋白含量。结果 益肾活血胶囊和叶酸等维生素均可明显降低血浆Hcy水平（P＜0.01），抑制血管内膜增厚，下调腹主动脉MCP1基因表达（P＜0.01），增加IκBα蛋白含量（P＜0.01）。益肾活血胶囊大剂量组疗效明显优于小剂量组和西药组（P＜0.05）。结论 益肾活血胶囊可明显降低血浆Hcy水平，抑制Hcy诱导的动脉粥样硬化的形成，其机制可能与下调MCP1基因表达，抑制NFκB活化有关。 【关键词】? 益肾活血胶囊；同型半胱氨酸；动脉硬化；单核细胞趋化蛋白1；核因子κB;核因子κB抑制因子α ? 　　To explore the effects of the Yishenhuoxue capsule (YC) on aortic monocyte chemoattractant protein1 (MCP1) mRNA expression and nuclear factorkappaB (NFκB) activation in atherogenesis of hyperhomocysteinemic rabbits. Methods? Forty male New Zealand white rabbits were divided into five groups: the control, the model, the low dose YC, the high dose?? YC and the western medicine (folic acid, VitB6 and VitB12) group. Apart from the control group, rabbits in other groups underwent balloon catheter injuries and a high methionine diet to induce hyperhomocysteinemia and atherosclerosis by treatment with different drugs. Plasma Hcy concentration, aortic morphological changes, MCP1 mRNA expression and expression of inhibitor of nuclear factorkappaB (IκBα) protein in the abdominal aorta were respectively determined by high performance liquid chromatography, HE staining, realtime quantitative PCR and western blot. Results? Both YC and western medicine could decrease the plasma Hcy concentration（P＜0.01), attenuate the intimal thickening, downregulate the MCP1 mRNA expression（P＜0.01) and increase the IκBα protein expression（P＜0.01). The efficacy of YC at a high dose was superior to that of YC at a low dose and western medicine（P＜0.05). Conclusions? YC decreases the plasma Hcy level and subsequently 　　同型半胱氨酸（Hcy）是一种含巯基氨基酸，是蛋氨酸代谢的中间产物。近年研究表明［12］血浆Hcy浓度升高是动脉粥样硬化（AS）及血栓栓塞性疾病的独立危险因素。Hcy致AS的机制与其诱发血管壁炎症反