中文摘要：

目的 研究吴茱萸碱对球囊损伤所致大鼠颈总动脉内膜增生的抑制作用,并探讨其可能的作用机制。方法 建立大鼠颈总动脉内膜球囊损伤模型,SD大鼠随机分为假手术组、模型组、吴茱萸碱低剂量（40 mg·kg^-1）和高剂量（80 mg·kg^-1）组。造模后第1天开始灌胃给药,每天1次,连续14 d10通过组织病理学观察颈动脉内膜增生状况,并计算颈动脉新生内膜面积（neointima area,NIA）、内膜/中膜（NIA/MA）比值;采用免疫组化法观察颈动脉增殖细胞核抗原（PCNA）的阳性表达、计算阳性率,评价吴茱萸碱抑制球囊损伤所致内膜增生效应;检测血浆一氧化氮（NO）、环磷酸鸟苷（c GMP）含量,运用逆转录-聚合酶链反应检测颈动脉血管颈动脉增殖细胞核抗原、内皮型一氧化氮合酶（e NOS）和平滑肌α-肌动蛋白（SMα-actin）mRNA的表达,探讨作用机制。结果 吴茱萸碱40和80 mg·kg^-1明显抑制球囊损伤所致血管内膜增生,降低内膜、内膜/中膜比值和颈动脉内膜颈动脉增殖细胞核抗原阳性表达率;明显升高球囊损伤所致大鼠血浆中一氧化氮和环磷酸尿苷含量的降低;下调颈动脉增殖细胞核抗原mRNA表达,上调内皮型一氧化氮合酶和平滑肌α-肌动蛋白mRNA的表达。结论 吴茱萸碱具有明显抑制球囊损伤所致大鼠颈动脉内膜增生的作用,其抑制作用与促进内皮型一氧化氮合酶活性,增加一氧化氮的生成,抑制血管平滑肌细胞增殖有关。

英文摘要：

OBJECTIVE To examine the inhibitory effects of evodiamine on vascular neointimal hyperplasia in balloon-in- jured carotid artery of rats and explore the possible mechanisms. METHODS Heahhy male Sprague Dawley rat vascular neointimal hyperplasia model was made by rubbing the endothelia of common carotid artery with a balloon, and then the rats were randomly divided into sham operation control group, model control group,evodiamine low（40 mg·kg^-1 ） and high（80 mg·kg^-1 ） dose groups. Evodiamine was intragastric administration for 14 consecutive days, and the sham operation or control rats were given with distilled water. After consecutive 14 d, the neointimal hyperplasia degree was observed by histopathological alterations and by calculating the proliferating cell nuclear antigen（PCNA） positive cells expression percentage in the common carotid artery. The levels of nitric oxide（NO） and cyclic guanosine monophosphate（cGMP） in plasma of rats were measured respectively. The mRNA expressions of PCNA, endothelial nitric oxide synthase（eNOS） and SM α-actin in carotid artery wall were analyzed separately by real time RT-PCR. RESULTS The neointimal hyperplasia was very serious, as evidenced by thickened neointima and narrowed lumen in carotid artery balloon-injured rats（ model control group）. Compared with the model control group, evodiamine 40 and 80 mg·kg^-1 administration could significantly ameliorate the histopathology of common carotid artery, decrease the positive expression rate of PCNA, but increase the levels of NO, cGMP in plasma of rats, downregulate the PCNA mRNA expression and upregulate mRNA expressions of eNOS and SM α-actin, respectively. CONCLUSION Evodiamine can depress the vascular neointimal hyperplasia induced by artery endothelia rubbing in rats, the mechanism may be related, at least partly, to the promotion of NO production.