醋柳黄酮对高同型半胱氨酸致兔动脉粥样硬化的抑制作用研究

Inhibitory Effects of Sindacon on Rabbits Atherosclerosis Induced by Hyperhomocysteinemia

目的:研究醋柳黄酮对高同型半胱氨酸(Hcy)致兔动脉粥样硬化(AS)的作用机制。方法:以球囊牵拉法损伤兔腹主动脉联合0.5%高蛋氨酸饲料喂养建立高Hcy血症致AS模型。将48只兔随机均分为空白对照组(生理氯化钠溶液)、模型组(生理氯化钠溶液)、阳性对照组(叶酸0.58 mg/kg、维生素B61.15 mg/kg、维生素B1228.75μg/kg)和醋柳黄酮低、中、高剂量组(0.32、0.76、1.6g/kg),每日灌胃给予相应药物1次,持续8周。末次给药后检测各组兔血浆中Hcy浓度,对腹主动脉进行苏木素-伊红(HE)染色观察AS的病理变化,用免疫组织化学测定腹主动脉中核因子-κB(NF-κB)及单核细胞趋化蛋白1(MCP-1)的表达。结果:与空白对照组比较,模型组兔血浆中Hcy浓度和腹主动脉中NF-κB、MCP-1表达均明显升高(P<0.01),血管内膜明显增厚,平滑肌细胞排列紊乱;与模型组比较,醋柳黄酮各剂量组和阳性对照组兔血浆中Hcy浓度和腹主动脉中NF-κB、MCP-1表达均明显降低(P<0.01),其中醋柳黄酮高剂量组较阳性对照组降低更明显(P<0.01);血管内膜增厚明显减轻,且与醋柳黄酮剂量呈正相关。结论:醋柳黄酮可通过抑制动脉斑块组织中NF-κB活化、降低MCP-1表达,从而抑制AS斑块的增殖。

OBJECTIVE：To investigate the mechanism of sindacon on rabbits atherosclerosis（AS）induced by high homocysteinemia（Hcy）. METHODS：High Hcy and AS model were induced by rabbit abdominal aorta damaged by balloon pull-through technique combined with 0.5% homomethionin diet. 48 rabbits were randomly divided into blank control group（physiological solution of sodium chloride）,model group（physiological solution of sodium chloride）,positive control group（folic acid 0.58 mg/kg,vitamin B61.15 mg/kg and vitamin B1228.75 μg/kg）,sindacon low-dose,medium-dose and high-dose groups（0.32,0.76,1.6 g/kg）.They were given relevant medicines intragastrically once a day for consecutive 8 weeks. After lasted medication,plasma concentration of Hcy in rabbits was determined;the morphology alteration of AS was observed by HE staining. The expression of NF-κ B and MCP-l in abdominal aorta was examined by immunohistochemistry. RESULTS：Compared with blank control group,plasma concentration of Hcy,the expression of NF-κB and MCP-1 were increased significantly in model group（P〈0.01）,and there were significant tunicae intima vasorum thickening and smooth muscle cell arrangement disorder. Compared with model group,plasma concentration of Hcy,the expression of NF-κ B and MCP-1 were decreased significantly in sindacon groups and positive control group（P〈0.01）,the decrease in sindacon high-dose group was more significant than in positive control group（P〈0.01）;and tunicae intima vasorum thickening was relieved significantly,which was positively correlated with the dose of sindacon. CONCLUSIONS：Sindacon can inhibit the proliferation of AS plaque by inhibiting the activation of NF-κB and decreasing the expression of MCP-1.