SREBP-1/小凹蛋白1介导烟酸姜黄素酯对ApoE-/-小鼠的抗动脉粥样硬化作用
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国家自然科学基金项目(31371161、81173047),湖南省自然科学基金项目(12JJ5068、2015JJ6077),湖南省“十二五”药学重点学科项目(2011年)


SREBP-1/Caveolin-1 Mediate the Anti-atherosclerotic Effect of Curcumin Nicotinate in Apolipoprotein E-Deficient Mice
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    目的探寻烟酸姜黄素酯对动脉粥样硬化病变的作用及机制。方法50只7周龄ApoE-/-小鼠,随机分为五组,即对照组、高脂组、辛伐他汀组[5mg/(kg·d)]、烟酸姜黄素酯低剂量组[33mg/(kg·d)]和烟酸姜黄素酯高剂量组(99mg/(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6周之后处死动物,检测血清中血脂水平;油红O染色法和HE染色法观察小鼠主动脉斑块及肝脏脂质蓄积;ELISA法检测血清中炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;Westernblot法检测小鼠肝脏中小凹蛋白1和SREBP-1的表达。结果与对照组相比,高脂组血清中总胆固醇(TC)和低密度脂蛋白胆固醇(LDLC)升高,高密度脂蛋白胆固醇(HDLC)降低,主动脉粥样硬化斑块增多。与高脂组相比,烟酸姜黄素酯组小鼠血清中的TC和LDLC明显降低,TNF-α和IL-6水平下降,而主动脉粥样硬化斑块减轻,肝脏脂质减少;烟酸姜黄素酯组肝脏小凹蛋白1蛋白表达高于高脂组,而SPEBP-1蛋白表达低于高脂组。结论烟酸姜黄素酯预防性给药能抑制高脂喂养所致的ApoE-/-小鼠动脉粥样硬化斑块的形成;机制可能与减少SREBP-1、增加小凹蛋白1蛋白水平,调节肝脏脂质代谢及炎症反应有关。

    Abstract:

    Aim To investigate the effects and mechanisms of Curcumin Nicotinate on the high fat diet(HFD) induced-atherosclerosis in ApoE-/- mice.Methods Seven weeks old male ApoE-/- mice were randomly divided into five groups(n50):control group,HFD group,simvastatin group (5 mg/(kg·d)),low doses of Curcumin Nicotinate group (33 mg/(kg·d)) and high doses of Curcumin Nicotinate group (99 mg/(kg·d)),gavaged every day,respectively.All the mice were fed up with high-fat,high-cholesterol diet that contained 5.0% fat (wt/wt) and 1.0% cholesterol except for control group.After six weeks of treatment,tissue specimens from liver,aorta and blood were collected.The serum total cholesterol (TC),triglyceride(TG),low density lipoprotein cholesterol (LDLC),high density lipoprotein cholesterol (HDLC) were detected by the automatic biochemical analyzer.The assessment of atherosclerosis in aortic trees and aortic sinus and the liver lipid were carried out by staining with oil red O.The atherosclerotic plaques in aortic arches were observed by HE staining.The serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured by ELISA kit.The expression of caveolin-1,SREBP-1 in liver were detected by Western blot.Results Compared with the control group,serum TC and LDLC were increased,while HDLC was decreased,and atherosclerotic plaques in aorta was significantly increased.After six weeks of treatment,Curcumin Nicotinate could reduce significantly the level of TC,LDLC,TNF-α and IL-6 in serum and reduce the area of atherosclerotic plaques in HFD ApoE-/- mice.The expression of caveolin-1 increased and SREBP-1 decreased in mice liver after Curcumin Nicotinate treatment compared with those in HFD group.Conclusions Curcumin Nicotinate alleviated the progression of atherosclerosis lesion in ApoE-/- mice,partly due to its regulation on lipid metabolism and inflammation of ApoE-/- mice by SREBP-1 and caveolin-1.

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龚勇珍,姚海伦,孙少卫,宋露萍,李荣东,熊燕,廖端芳. SREBP-1/小凹蛋白1介导烟酸姜黄素酯对ApoE-/-小鼠的抗动脉粥样硬化作用[J].中国动脉硬化杂志,2014,22(12):1189~1194.

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  • 收稿日期:2014-09-25
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