南蛇藤素对载脂蛋白E基因敲除小鼠斑块内胶原、巨噬细胞移动抑制因子和基质金属蛋白酶9表达的影响  

Effects of Celastrol on the Collagen,Macrophage Migration Inhibitory Factor and Matrix Metalloproteinase-9 Expressions in the Plaque of ApoE Gene Knockout Mice

作　　者：李金平[1] 程军[1] 田卓[1] 胡厚源[1] 

机构地区：[1]第三军医大学西南医院心内科,重庆市400038

出　　处：《中国动脉硬化杂志》2008年第10期801-804,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(30770851)

摘　　要：目的观察南蛇藤素对载脂蛋白E基因敲除小鼠斑块中胶原、巨噬细胞移动抑制因子和基质金属蛋白酶9表达的影响。方法8周龄雄性载脂蛋白基因敲除小鼠12只,随机分为南蛇藤素干预组和动脉粥样硬化模型组,每组各6只,同龄的雄性C57BL/6J小鼠6只作为正常对照,各组均给以高脂饮食饲养8周,在高脂饲养的后4周,分别予以南蛇藤素和相当剂量的溶剂二甲基亚砜腹腔注射,每日1次,连续用药4周;处死后行主动脉连续石蜡切片、HE染色观察组织形态学改变,苦味酸-天狼星红染色检测斑块内胶原含量,免疫组织化学方法观察主动脉斑块内巨噬细胞移动抑制因子和基质金属蛋白酶9蛋白表达的强度。结果模型组形成了早期斑块,南蛇藤素组斑块面积较模型组明显减小,分别为4270.74±1027.64μm2和8971.19±1665.76μm2(P<0.01),南蛇藤素组斑块内胶原含量显著高于模型组(平均光密度分别为0.0275±0.0068和0.0142±0.0054,P<0.01);南蛇藤素组与模型组比较斑块内基质金属蛋白酶9表达明显降低(平均光密度分别为0.0054±0.0020和0.0263±0.0080,P<0.001),巨噬细胞移动抑制因子的表达也明显降低(平均光密度分别为0.0114±0.0016和0.0227±0.0039,P<0.001)。结论南蛇藤素可能通过下调载脂蛋白E基因敲除小鼠斑块内基质金属蛋白酶9和巨噬细胞移动抑制因子表达,抑制胶原的降解进而发挥抗动脉粥样硬化及稳定斑块作用。Aim To investigate the effects of celastrol on the collagen macrophage migration inhibitory factor and matrix metalloproteinase-9 expressions in the plaque of apoE gene knockout mice gene knockout mice. Methods 8- week old apoE gene knockout mice, male , were divided randomly into atherosclerosis model group and celastrol treantment group （ n = 6 in each group）. 8-week old male C57BL/6J mice were the normal control. The mice in celastrol group were given, celastrol 2 mg/（ kg ·d ） by intraperitoneal injection for 4 weeks ; the mice in control group were only given equivalent amount of dimethyl sulfoxide （ DMSO ）, and the contents of collagen in the aortic atherosclerotic lesions were detected with Picrosirius Red staining. The expression of macrophage migration inhibitory factor and MMP-9 were detected by immunological histochemical method. Results The area of lipid plaque in the mice treated with celastrol was 4270.74 ± 1027.64 μm2, significantly smaller than that of the model group 8971.19±1665.76 μm2 （ P 〈 0.01 ）. The contents of collagen in the atherosclerotic plaque was significantly higher in Celastrol group compared with model group （ mean optical density ： 0. 0275 ± 0. 0068 vs 0.0142± 0. 0054, P 〈 0.01 ）. The expression of matrix metalloproteinase-9 was significantly decreased in celastrol group compared with the model group （ mean optical density： 0.0054 ± 0. 0020 vs 0.0263 ± 0. 0080, P 〈 0. 001 ）. The expression of macrophage migration inhibitory factor was also significantly decreased in celastrol group compared with the model tgroup （mean optical density： 0.0114 ± 0. 0016 vs 0. 0227 ± 0. 0039, P 〈 0. 001 ）. Conclusions Celastrol can inhibit the progress of atherosclerotic plaque and promote the stability of ather-oscl erotic plaque in apoE gene knockout mice , which might be relative to its inhibition on the degradation of collagen and expression of macrophage migration inhibitory factor, matrix metalloproteinase-9 in atherosclerotic plaque of apoE g

关 键 词：病理学与病理生理学 动脉粥样硬化 南蛇藤素 载脂蛋白E基因敲除小鼠 胶原 巨噬细胞 移动抑制因子 基质金属蛋白酶9 

分 类 号：R363[医药卫生—病理学]