小凹蛋白1-NFκB通路介导乙酰水杨酸姜黄素酯的抗动脉粥样硬化作用  

Caveolin-1/nuclear factor kappa B pathway mediates antiatherosclerotic effect of curcumin acetylsalicylate in apolipoprotein E-deficient mice

作　　者：龚勇珍[1] 孙少卫[2] 杨慧仙[2] 宋露萍[2] 姚海伦[2] 夏伯候[2] 林丽美[2] 李荣东[2] 熊燕[3] 廖端芳[2] 

机构地区：[1]中南大学药学院药理教研室,湖南长沙410078 [2]湖南中医药大学干细胞中药调控与应用研究室,湖南长沙410208 [3]广州医科大学蛇毒研究所,广东广州510182

出　　处：《中国现代医学杂志》2015年第9期21-26,共6页China Journal of Modern Medicine

基　　金：国家自然科学基金项目(No:31371161;No:81173047);湖南省自然科学基金项目(No:2015JJ6077);湖南省"十二五"药学重点学科(2011年)

摘　　要：目的探讨乙酰水杨酸姜黄素酯对动脉粥样硬化病变的作用及机制。方法 40只7周龄Apo E-/-小鼠,随机分为对照组、高脂组、辛伐他汀组[5 mg/(kg·d)]、乙酰水杨酸姜黄素酯低剂量组[23.8 mg/(kg·d)]和乙酰水杨酸姜黄素酯高剂量组[71.5 mg/(kg·d)],其中对照组给予普通饲料,其他组给予高脂饲料喂养。连续干预4周之后处死动物,检测血清中血脂水平;油红O染色法观察小鼠主动脉斑块;ELISA法或免疫组化法检测血清和肝脏炎症因子TNF-α、IL-6水平;Western blot检测小鼠肝脏中小凹蛋白1和NFκB p65的表达。结果与对照组相比,高脂组血清中TC和LDL-C升高,HDL-C降低,主动脉粥样斑块增多。与高脂组相比,乙酰水杨酸姜黄素酯组小鼠血清中的TC和LDL-C降低,肝脏脂质减少,血清和肝脏炎症因子水平下降,而主动脉粥样硬化斑块减轻;肝脏小凹蛋白1水平升高而NFκB p65水平降低。结论乙酰水杨酸姜黄素酯能抑制高脂喂养所致的Apo E-/-小鼠动脉硬化斑块的形成;机制可能与增加肝脏小凹蛋白1、减少NFκB p65蛋白水平,调节肝脏脂质代谢及炎症反应有关。【Objective】To investigate the effects and mechanisms of curcumin acetylsalicylate on the high-fat diet（HFD） induced-atherosclerosis in apolipoprotein E-deficient（Apo E-/-） mice. 【Methods】Forty seven-week old male Apo E-/- mice were randomly divided into five groups（8 in each group）： control group, HFD group, simvastatin group [5 mg/（kg·d）], low doses of curcumin acetylsalicylate group [23.8 mg/（kg·d）] and high doses of curcumin acetylsalicylate group [71.5 mg/（kg·d）], gavaged every day, respectively. All the mice were fed with high-fat, highcholesterol diet that contained 5.0% fat（wt/wt） and 1.0% cholesterol except for the control group. After four weeks of treatment, tissue specimens from liver, aorta and blood were collected. The serum TC, LDL-C and HDL-C were measured by the automatic biochemical analyzer. The sections of aortic sinus were stained with oil red O for assessment of atherosclerosis. The TNF-α and IL-6 levels in serum and liver were measured by ELISA and immunohistochemistry assay, respectively. The expressions of caveolin-1 and nuclear factor kappa B（NFκB） p65 in liver were detected by Western blot. 【Results】The serum TC, LDL-C and aorta atherosclerotic plaques increased while the serum HDL-C decreased in the HFD group compared with the control group. Curcumin acetylsalicylate treatment reduced the levels of TC, LDL-C, TNF-α and IL-6 in serum and also the area of atherosclerotic plaques, and the expression of caveolin-1 increased while NFκB p65 and TNF-α decreased in liver after treatment compared with those in the HFD group.【Conclusions】Curcumin acetylsalicylate can alleviate the progression of atherosclerosis lesion in Apo E-/- mice, partly due to its regulation on lipid metabolism and inflammation of Apo E-/- mice by NFκB p65 and caveolin-1.

关 键 词：乙酰水杨酸姜黄素酯 动脉粥样硬化 小凹蛋白1 核因子κB 载脂蛋白E敲除小鼠 

分 类 号：R966[医药卫生—药理学]