甲状旁腺激素相关蛋白在兔颈动脉外膜损伤致动脉粥样硬化中的作用  

Role of parathyroid hormone-related protein in rabbit carotid atherosclerosis induced by removal of adventitia

作　　者：姚睿荣[1] 高琳[1] 梁春[1] 陈金明[1] 潘晓明[1] 吴宗贵[1] 

机构地区：[1]第二军医大学第二附属医院心内科,上海200003

出　　处：《上海医学》2009年第4期289-292,I0001,共5页Shanghai Medical Journal

基　　金：国家重点基础研究发展计划(973计划)资助项目(2005CB523309)

摘　　要：目的观察甲状旁腺激素相关蛋白(PTHrP)(1～34)在兔颈动脉外膜损伤致动脉粥样硬化(AS)中的作用。方法雄性新西兰大白兔给予基础饲料喂养1周、高脂喂养4周后去除左侧颈动脉外膜,随机分成4组,分别接受蒸馏水灌胃(4mL/d,对照组)、阿托伐他汀混悬液灌胃(5mg·kg-1.d-1,阿托伐他汀组)、颈动脉局部予1mLF-127凝胶(空白凝胶组)或予1mL1μmol/LPTHrP(1～34)凝胶干预(PTHrP组),右侧颈动脉以0.9%氯化钠溶液处理,不损伤外膜,作为对照侧。继续高脂喂养4周后处死,取标本,苏木精-伊红(H-E)染色检测AS斑块,测定颈动脉内膜/中膜面积比(IMR),免疫组织化学染色检测颈动脉PTHrP(1～34)的表达情况。结果各组内损伤侧动脉的IMR均显著高于对照侧(P值均<0.05)。各组间损伤侧动脉的IMR比较,PTHrP组显著高于其他3组(P值均<0.05),阿托伐他汀组显著低于其他3组(P值均<0.05)。各组颈动脉标本均可见染成棕黄色的PTHrP(1～34)阳性表达信号,主要存在于外膜和内膜粥样斑块区,肩部表达更多,中膜有少量表达。PTHrP组的PTHrP免疫组织化学阳性表达比例显著高于其他3组(P值均<0.05),阿托伐他汀组显著低于其他3组(P值均<0.05)。结论局部给予PTHrP(1～34)可促进AS的发展,阿托伐他汀可通过下调PTHrP(1～34)的表达而抑制血管外膜损伤所致AS的进展。Objective To investigate the role of parathyroid hormone-related protein （PTHrP） in atherosclerosis induced by removal of adventitia. Methods Male New Zealand rabbits were given baseline diet for one week and high-cholesterol diet for four weeks, then the left carotid adventitia were removed with collagenase. Animals were randomly divided into four groups according to what they received： water （i. g., 4mL/d）, atorvastatin （i.g., 5 mg·kg^-1·d^-1, F-127 gel （thyroid artery, 1 mL）, and PTHrP（1-34） （thyroid artery, 1 mL 1μmol/L） groups. The right thyroid arteries of animals, receiving 0.9% saline and receiving no resection, were taken as control. The animals were fed with high-cholesterol diet for another four weeks before they were sacrificed. The AS samples were collected and subjected to Hematoxylin-Eosin staining. The intimal-to-medial area ratio （IMR） of thyroid artery was determined. The expression of PTHrP （1 -34） was detected immunohistochemically. Results The IMR of the injured arteries in each group were significantly higher than those of the control sides （all P〈 0.05）. The IMR ratio of PTHrP group was significantly higher than those of the other three groups （all P〈0.05） ; that of the atorvastatin group was significantly lower than those of the other three groups （all P〈0.05）. PTHrP （1- 34） expressed in atherosclerotic plaques in each group, especially in the plagues between the intima and media and on the shoulder. The positive rate of PTHrP in PTHrP group was significantly higher than the other three groups （all P〈0.05）, and that of the atorvastatin group was significantly lower than those of the other groups （all P〈0.05）. Conclusion Locally applied PTHrP（1 -34） can promote atherosclerosis formation. Atorvastatin can inhibit atherogenesis by removal of adventitia in part by lowering blood total cholesterol level and the expression of PTHrP（1-34）.

关 键 词：甲状旁腺激素相关蛋白 动脉粥样硬化 炎症 阿托伐他汀 

分 类 号：R543.5[医药卫生—心血管疾病]