氯吡格雷对尼古丁诱导的血管内皮损伤的保护作用  

Protective effect of clopidogrel against nicotine-induced vascular endothelial dysfunction in rats

作　　者：聂亚雄[1] 尹剑[1] 黄如训[2] 高帆[1] 朱云龙[1] 杨宏文[1] 谢明[1] 

机构地区：[1]南华大学附属第一医院神经科,衡阳421001 [2]中山大学附属第一医院神经科

出　　处：《中华老年心脑血管病杂志》2010年第7期637-640,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：湖南省自然科学基金(08JJ3036);湖南省科技厅计划项目(06106);衡阳市科技局课题(06Kj23)

摘　　要：目的探讨尼古丁对血管内皮细胞的影响及氯吡格雷的保护作用。方法将40只SD大鼠分为5组,对照组、模型组(尼古丁2 mg/kg)、尼古丁损伤+氯吡格雷低剂量组(低剂量组)、尼古丁损伤+氯吡格雷中剂量组(中剂量组)、尼古丁损伤+氯吡格雷高剂量组(高剂量组),每组8只。尼古丁造模4周后,测定大鼠血浆超氧化物歧化酶(SOD)、内皮素1、NO及内皮型一氧化氮合酶(eNOS)浓度,免疫组织化学法及Western blot法测定血管eNOS阳性细胞的表达。结果与对照组比较,模型组大鼠血浆NO、eNOS及SOD浓度明显下降,而内皮素1浓度明显上调,eNOS阳性细胞表达明显减少(P<0.01);与模型组比较,低、中、高剂量组大鼠NO、eNOS及SOD浓度明显升高,eNOS阳性细胞表达明显增多,且中、高剂量组大鼠增多更显著(P<0.05,P<0.01)。结论氯吡格雷可能抑制氧化应激反应,调节内皮细胞中eNOS的正常表达,从而缓解尼古丁对血管内皮细胞的损害。Objective To investigate the protective effect of clopidogrel against vascular endothelial injury induced by nicotine in rats. Methods A total of 40 SD rats were randomized into 5 groups. control group, model group（nicotine 2 mg/kg）, low-dose elopidogrel group, middle-dose clopidogrel group,high-dose clopidogrel group. After treatment for 4 weeks, the plasma SOD,ET-1, NO and eNOS levels were measured. The expression of vascular endothelial eNOS was detected by immunohistochemistry and Western blot. Results Compared with control group, concentrations of SOD, NO and eNOS and expression of eNOS-positive cells of model group decreased, while the concentration of ET-1 increased （P 〈 0.01）. Compared with model group, the plasma SOD,NO and eNOS levels of clopidogrel groups increased,the eNOS-positive cells of chest aortic endothelial cells increased,and those of the middle- and high-dose clopidogrel groups were more remarkable （P 〈0.05,P 〈 0.01）. Conclusion Clopidogrel may regulate the normal expression of eNOS in blood vessels through inhibiting the nicotine-induced oxidative stress, so that the endothelial cell contraction factor and relaxation factor tend to be balanced,thereby significantly alleviating the damage of vascular endothelial cells.

关 键 词：内皮 血管 尼古丁 超氧化物歧化酶 一氧化氮 一氧化氮合酶 氯吡格雷 

分 类 号：R965[医药卫生—药理学]