凝集素样氧化低密度脂蛋白受体1在兔自体静脉移植物及其粥样硬化病变中的分布表达

Increased lectin-like oxidized low density lipoprotein receptor-1 expression in the autologous vein grafts and vein graft atherosclerosis

目的自体静脉移植物粥样硬化的产生机制有其特殊性,我们研究了一种新的氧化低密度脂蛋白(OXLDL)的受体,即凝集素样氧化低密度脂蛋白受体1(LOX1)在兔自体静脉移植物及其粥样硬化病变中的表达,探讨其在静脉移植物粥样硬化形成中的作用。方法将30只新西兰大白兔随机分为正常对照组、单纯移植组和高脂移植组3组,分别给予普通饲料喂养(N=10)、单纯自体颈外静脉移植(N=10)和自体颈外静脉移植加高脂饲料喂养(N=10)。在实验12周末处死动物,静脉移植段行免疫组化染色检测LOX1的表达及分布,用半定量逆转录聚合酶链反应(RTPCR)检测LOX1MRNA表达的情况,并且统计分析血清总胆固醇水平、内膜厚度与LOX1的表达之间的关系。结果正常对照组的颈外静脉组织中仅见极少量LOX1表达于静脉内皮细胞表面;而单纯移植组的静脉移植物的新生内膜和内皮细胞层,可见LOX1的表达明显升高(0.31±0.14比0.09±0.04,P<0.01),其中LOX1表达最强的是内皮细胞;高脂移植组静脉移植物的内皮和粥样硬化部位,可见LOX1的表达更加显著上调(0.93±0.34比0.31±0.14,P<0.01),在粥样硬化部位,内皮细胞和泡沫细胞LOX1染色均阳性,而表达最强的也是内皮细胞。并且LOX1的表达和血清总胆固醇水平、内膜厚度均显著正相关(P=0.00和0.02),偏相关系数分别为0.78和0.42。结论LOX1表达于兔自体静脉移植物的内皮和新生内膜,表达量较正常静脉组织明显上调,高胆固醇血症可以上调静脉移植物粥样硬化部位LOX1的表达,提示LOX1可能参与了静脉移植物粥样硬化的发生发展。

Objective To study the changes of lectin-like oxidized low density lipoprotein receptor-1 （ LOX-1 ） expression in the autologous vein grafts and vein graft atherosclerotic lesions. Methods Thirty New Zealand white rabbits were randomly assigned to normal control group （rabbits fed with normal diet, n = 10）, vein graft group （autologous external jugular vein grafting to common carotid artery and fed with normal diet, n = 10） or vein graft plus high-lipid diet group （ autologous vein graft and fed with high-lipid diet, n = 10） for 12 weeks. LOX-1 expressions in the grafts were examined by immunohistochemistry and semi-quantitative reverse transcription-PCR. The relationships between serum total cholesterol level, intimal thickness and LOX-1 expression were also investigated. Results LOX-1 expression was low in the endothelium of external jugular veins in the normal control group and significantly increased in the endothelium and neointima of vein grafts in the vein graft group （0. 31±0. 14 vs. 0. 09 ±0. 04, P 〈0. 01 ） and which was further increased in the endothelium and atherosclerotic lesions in the vein graft plus highlipid diet group （0. 93 ±0. 34 vs. 0. 31 ±0. 14, P 〈0. 01 ）. LOX-1 expression in the atherosclerofic lesions was located both in endothelial cells and foam cells and the expression was most prominent in endothelial cells. LOX-1 expression and intimal thickness were positively related to serum total cholesterol level （P = 0. 00 and 0. 02 ） and the partial correlation coefficient was 0. 78 and 0. 42, respectively. Conclusions LOX-1 expression is increased in endothelium and neointima of autologous vein grafts of rabbits. Hypercholesterolemia upregulates LOX-1 expression in vein graft atherosclerosis. Thus, LOX-1 might play an important role in the pathogenesis of vein graft atherosclerosis.