氟伐他汀单用及与醛固酮拮抗剂联用对兔颈动脉粥样硬化HS-CRP及MMP-9的影响  

The effect of fluvastatin alone and associated with aldosterone antagonism for carotid atherosclerosis in rabbits

作　　者：刘文华[1] 黄怀宇[1] 顾承志[1] 黄志东[1] 朱向阳[1] 刘春[2] 

机构地区：[1]南通大学第二附属医院神经内科,江苏南通226001 [2]南通大学实验动物中心,江苏南通226001

出　　处：《中风与神经疾病杂志》2007年第5期527-529,641,共4页Journal of Apoplexy and Nervous Diseases

基　　金：江苏省卫生厅重点攻关课题(H200217)

摘　　要：目的探讨他汀类药物单用及联用醛固酮拮抗剂对兔颈动脉粥样硬化的作用机制。方法高脂饲养建立兔颈动脉硬化斑块模型。将兔分为对照组、高脂组、氟伐他汀干预组(治疗1组)及氟伐他汀加安体舒通干预组(治疗2组)。采用酶联免疫吸附法(ELISA)检测血清中超敏C反应蛋白(hs-CRP)的含量,用免疫组织化学法检测MMP-9表达量,HE染色观察颈动脉粥样硬化斑块结构变化。结果高脂组hs-CRP及MMP-9水平高于对照组(P<0.01),且8周、12周高脂组多于4周组(P<0.01)。在治疗1组中12周组hs-CRP及MMP-9水平低于对应的4周组(P<0.01)。在治疗2组中8、12周组hs-CRP及MMP-9水平低于对应的4周组(P<0.01)。治疗1、2组与对照组、高脂组在各时间段组间比较hs-CRP及MMP-9水平低,均有显著性差异(P<0.01);治疗2组中8周与12周hs-CRP及MMP-9水平低于1对应组(P<0.05～0.01)。结论随高脂饲养时间延长,血清中hs-CRP的含量及动脉斑块中MMP-9表达量升高;他汀类药物通过降低hs-CRP的含量及MMP-9表达量延缓动脉硬化形成及易损斑块产生,联用醛固酮拮抗剂时此作用增强。Objective To explore the protective effects and mechanism of fluvastatin and associated with aldosterone antagonism for rabbit carotid artery atherosclerosis. Methods The rabbit carotid atherosclerosis（CAS） models was established through the inducement of high cholesterol. The rabbits were divided into control group, high cholesterol group,the first therapy group with fluvastatin and the second therapy group associated with aldosterone antagonism. The rabbits were killed in 4th,Sth and 12th weeks respectively after feeding to obtain the vulnerary plaques to detect the concentration of high sensitive C-reactive protein （hs-CRP）through ELISA, matrix metalloproteinase-9 （MMP-9）expression evaluated by immunohistochemistry and the changes of morphology observed by HE staining. Results The levels of hs-CRP and MMP-9 in the high cholesterol group was higher than the control group （P〈0.01）;furthermore,in the 8th and 12th weeks treatment group was higher than the 4th weeks group in the high cholesterol group （P〈0.01）. The levels of hs-CRP and MMP-9 of the 12th weeks groups were lower than the corresponding 4th weeks group in the first therapy group （P〈0. 01）. The levels of hs-CRP and MMP-9 of the 8th and 12th weeks groups were lower than the corresponding 4 weeks group in the second therapy group （P〈0.01）. The levels of hs-CRP and MMP-9 of the first and second therapy group were lower than the control group and high cholesterol group in 4th,8th and 12th weeks respectively （P〈0. 01）. The levels of hs-CRP and MMP-9 of the 8th, 12th weeks groups of the second therapy group was lower than the corresponding group in the first therapy group （P〈0.05～0.01）. Conclusion With the delay of high cholesterol feeding,the concentration of hs-CRP of serum and MMP-9 expression of carotid artery plaque（CAP）were enhanced. Fluvastatin could delay formation of damageable CAP through decreasing hs-CRP and MMP-9 expression. The effects could be enhanced when fluvastatin associated with aldost

关 键 词：颈动脉硬化 超敏C反应蛋白 基质金属蛋白酶-9 氟伐他汀 醛固酮拮抗剂 

分 类 号：R543.5[医药卫生—心血管疾病]