凝集素样氧化低密度脂蛋白受体在兔自体静脉移植物粥样硬化病变中的表达及洛沙坦干预作用的研究  

Upregulation of lectin-like oxidized low density lipoprotein receptor-1 expres sion contributed to the vein graft atherosclerosis: modulation by losartan

作　　者：黄东[1] 葛均波[1] 梁春[2] 罗育坤[1] 贾庆哲[1] 王克强[1] 

机构地区：[1]复旦大学附属中山医院上海市心血管病研究所,上海200032 [2]第二军医大学附属长征医院心内科

出　　处：《中华心血管病杂志》2004年第10期915-918,共4页Chinese Journal of Cardiology

基　　金：国家重点基础研究发展规划 ( 973 )资助项目 (G2 0 0 0 0 5 690 3 )

摘　　要：目的　探讨凝集素样氧化低密度脂蛋白受体 (LOX 1)在静脉移植物粥样硬化中的表达及洛沙坦抗静脉移植物粥样硬化的作用。方法　 30只雄性新西兰大白兔行自体颈外静脉移植术后 ,随机分为高胆固醇组 (HC组 ,n =10 ) ,洛沙坦组 (LHC组 ,n =10 )和对照组 (C组 ,n =10 ) ,分别给予高胆固醇饮食、高胆固醇饮食加洛沙坦和正常饲料喂养。在实验 12周末处死动物 ,检测血脂水平 ,同时静脉移植段行HE染色计算内膜增厚程度 ,免疫组化染色检测LOX 1的分布 ,用半定量逆转录多聚酶链式反应检测LOX 1mRNA表达的情况。结果　实验各组的静脉移植物均发现以显著内膜增厚为表现形式的新生内膜过度增生。而在HC组可见在显著内膜增厚基础上发生的典型的粥样硬化病变 ,洛沙坦可减小粥样硬化病灶范围及粥样斑块不稳定程度。C组的内皮和新生内膜可见LOX 1少量表达 ,HC组的内皮和粥样硬化部位LOX 1的表达显著上调 (0 93± 0 34比 0 31± 0 14 ,P <0 0 1) ,而洛沙坦可以下调这种由高脂引起的LOX 1的高表达 (0 5 2± 0 2 1比 0 93± 0 34,P <0 0 1)。结论　LOX 1表达于兔自体静脉移植物的内皮和新生内膜 ,高胆固醇血症可以上调静脉移植物粥样硬化部位LOX 1的表达 ,洛沙坦能够通过下调LOXObjective To study the expression of lectin-like oxidized low density lipoprotein recepto r-1 (LOX-1) in the autologous rabbit vein graft and the modulating anti-ather osclerotic effect of losartan (a specific type 1 angiotensin II receptor antagon ist). Methods Autologous external jugular veins were grafted to common carotid arteries in 30 male New Zealand white rabbits. After surgery, rabbits were randomly assinged into 3 groups (10 rabbits in each): (1) HC group (fed with high cholesterol diet); (2) LHC group (fed with high cholesterol diet puls losartan of 10 mg·kg_-1·d_-1); (3) control group (fed with reg ular chow). All the animals were sacrificed at the end of 12th week. Serum lipi d levels were measured and vein grafts intimal thickening was quantitated in HE stained segments. LOX-1 mRNA expressions in the grafts were examined by immunoh istochemistry and semi-quantitative reverse transcription-PCR. Result s Neointimal hyperplasia was observed in all vein grafts characterized by extensive intimal thickening. Typical atherosclerotic lesions were found in vein grafts of HC group which were attenuated by losartan. Losartan also reduc ed the size of the lesion and lessened the vulnerability of the atherosclerotic plaque of vein grafts. A modest LOX-1 expression was shown in the endothelium a nd neointima of vein grafts in the control group. LOX-1 expression was signifi cantly upregulated in the endothelium and atherosclerotic lesions in HC group(0 .93±0.34 vs. 0.31±0.14,P<0.01), and losartan downregulated the LOX -1 expression caused by high lipidemia (0.52±0.21 vs. 0.93±0.34,P<0 .01). Conclusion LOX-1 is expressed in endothelium and neoi ntima of autologous vein graft of rabbits. Hypercholesterolemia upregulates LOX -1 expression in vein graft atherosclerosis. Losartan could attenuate the vein graft atherosclerosis through the downregulation of LOX-1 expression.

关 键 词：粥样硬化 洛沙坦 表达 静脉移植物 自体静脉移植 新生内膜 氧化低密度脂蛋白 LOX 凝集素 雄性 

分 类 号：R654.2[医药卫生—外科学]