普罗布考与塞来昔布联合应用对大鼠动脉粥样硬化的影响
Effect of probucol combined with celecoxib on atherosclerosis in rats
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摘要: 目的:探讨普罗布考与塞来昔布联合应用对大鼠动脉粥样硬化的影响。方法:SD雄性大鼠 40只, 随机分为正常组、模型组、普罗布考组、塞来昔布组及普罗布考与塞来昔布联合组(联合组), 每组各8只。正常组给予基础饲料喂养, 模型组为建立动脉粥样硬化模型, 予以高脂饲料+维生素D3+动脉内膜球囊损伤术, 普罗布考组、塞来昔布组、联合组同法造模后分别予以普罗布考、塞来昔布、普罗布考联合塞来昔布灌胃。药物干预12周后, 检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C), 酶联免疫吸附试验法检测血清C反应蛋白(CRP)和正五聚体蛋白3(PTX3), HE染色观察胸主动脉的病理形态改变并计算动脉内膜、中膜厚度及内膜/中膜厚度比。结果:与正常组比较, 模型组、普罗布考组、塞来昔布组和联合组的TC、LDL-C、CRP均明显升高(P<0.01);与模型组比较, 普罗布考组和联合组的TC、LDL-C、CRP、PTX3均显著降低(P<0.01);与正常组比较, 普罗布考组、塞来昔布组和联合组的内膜厚度、中膜厚度、内膜/中膜厚度比均明显增加(P<0.01), 普罗布考组、塞来昔布组和联合组与模型组比较, 内膜厚度、内膜/中膜厚度比均显著减小, 中膜厚度增加(P<0.01)。结论:普罗布考和塞来昔布联合应用可明显降低动脉粥样硬化大鼠血脂和炎性因子水平, 有一定的抗动脉粥样硬化作用。Abstract: Objective:To investigate the effects of probucol combined with celecoxib on atherosclerosis in rats.Methods:Forty male SD rats were randomly divided into the normal group, model group, probucol group, celecoxib group and probucol combined with celecoxib group(8 rats each group).Normal group was fed with standard forage.Rat model with atherosclerosis was established, and treated with high lipid, Vitamin D3 plus balloon injury of endarterium.The probucol group, celecoxib group and probucol combined with celecoxib group were treated with oral gavage, respectively.After 12 weeks of drug intervention in all groups, the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C) and high density lipoprotein-cholesterol(HDL-C) were detected, the levels of serum C-reactive protein(CRP) and Pentraxin3(PTX3) were determined by ELISA, and the pathomorphological changes of thoracic aorta were measured using HE staining and the thickness of arterial intima and media and thickness ratio of intima to media were calculated.Results:Compared with the normal group, the serum levels of TC, LDL-C and CRP in model group, probucol group, celecoxib group and probucol combined with celecoxib group significantly increased(P<0.01).Compared with the model group, the serum levels of TC, LDL-C, CRP and PTX3 in probucol group and probucol combined with celecoxib group significantly decreased(P<0.01).Compared with the normal group, the thickness of arterial intima and media, and thickness ratio of intima to media in probucol group, celecoxib group and probucol combined with celecoxib group significantly increased(P<0.01).Compared with the model group, the thickness of arterial intima and thickness ratio of intima to media significantly decreased and the thickness of arterial media significantly increased in probucol group, celecoxib group and probucol combined with celecoxib group(P<0.01).Conclusions:The combination use of probucol and celecoxib can significantly decreased the levels of serum lipids and inflammatory factors in rats with atherosclerosis, which has certain effects on anti-atherosclerosis.
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Key words:
- atherosclerosis /
- probucol /
- celecoxib /
- rat
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[1] Ross R.Atheroscleresis:an inflammatory disease[J].N Engl J Med,1999,340(2):115-126. [2] Libby P, Ridker PM,Maseri A.Inflammation and atherosclerosis[J].Circulation,2002,105(9):135-143. [3] Manduteanu I,Simionescu M.Inflammation in atherosclerosis:a cause or a result of vascular disorders?[J].J Cell Mol Med,2012,16(9):1978-1990. [4] Kaplan M,Hamoud S,Tendler Y,et al.A significant correlation between C - reactive protein levels in blood monocytes derived macrophages versus content in carotid atherosclerotic lesions[J].J Inflamm(Lond),2014,11(1):7. [5] Kaptnge S,Di Angelantonio E,Lowe G,et al.C-reactive protein concentration and risk of coronary heart disease,stroke,and mortality:individual participant mela-analysis[J].Lancet,2010,375(9709):132-140. [6] Inoue K, Kodama T, Daida H.Pentraxin 3:a novel biomarker for inflammatory cardiovascular disease [J].Int J Vasc Med,2012, 2012:657025. [7] 刘华,方唯一,袁方,等.Pentraxin 3蛋白在兔动脉粥样硬化斑块中的表达[J].上海交通大学学报:医学版,2011,31(3):271-274. [8] Peri G,Introna M,CorradiD,et al.PTX3,aprototypic long pentraxin,is an early indicator of acute myocardial infarction in humans[J].Circulation, 2000,102(6):636-641. [9] Matsui S,Ishii J,Kitagawa F,et al.Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction [J].Atherosclerosis,2010,210(1):220-225. [10] 郭延松,吴宗贵,杨军柯,等.三种大鼠动脉粥样硬化模型复制方法的比较[J].中国动脉硬化杂志,2003,11(5):465-469. [11] Kereiakes DJ.Improving adjunctive pharmacotherapy for primary percutaneous coronary intervention in ST-segment elevation myocardial infarction:beyond the HORIZONS-AMI trial [J].Rev Cardiovasc Med,2009,10(2):72-82. [12] Schafers M,Schober O,Hermann S.Matrix-metalloproteinase as imaging targets for inflammatory activity in atherosclerotic plaques[J].J Nucl Med,2010,51(5):663-666. [13] Kenich I,Chiaki I,Kenichi T,et al.Probucol enhances the expression of human hepatic scavenger receptor class B type Ⅰ,possibly through a species-specific mechanism [J].Arterioscler Thromb Vasc Biol,2005,25(11):2422-2427. [14] Tang SY,Monslow J,Todd L,et al.Cyclooxygenase-2 in endothelial and vascular smooth muscle cells restrains atherogenesis in hyperlipidemic mice [J].Circulation,2014,129(17):1761-1769. [15] Hong TT,Huang J,Barrett TD,et al.Effects of cyclooxygenase inhibition on canine coronary artery blood flow and thrombosis [J].Am J Physiol Heart Circ Physiol,2008,294(1):145-155. [16] 郭远林,陈纪林,李建军, 等.塞来昔布与小剂量阿司匹林合用对动脉粥样硬化的影响[J].中国动脉硬化杂志,2005,13(2):167-170. -
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