南蛇藤素对载脂蛋白E基因敲除小鼠主动脉壁C反应蛋白及组织因子表达的影响  

Effects of Celastrol on the Expression of C-reactive Protein and Tissue Factor in the Aorta of ApoE Gene Knockout Mice

作　　者：程军[1] 李金平[1] 田卓[1] 胡厚源[1] 

机构地区：[1]中国人民解放军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5期341-344,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30770851)

摘　　要：目的探讨南蛇藤素对高脂饲养载脂蛋白E基因敲除小鼠在动脉粥样硬化病变形成的早期动脉壁内C反应蛋白和组织因子表达的影响。方法8周龄雄性载脂蛋白E基因敲除小鼠12只,随机分为南蛇藤素干预组或二甲基亚砜溶剂对照组,每组各6只。均给予高脂饲养8周,在高脂饲养的后4周,分别给予南蛇藤素2mg/(kg·d)或相当剂量的二甲基亚砜腹腔注射。麻醉处死小鼠后,取小鼠主动脉,以石蜡包埋,行主动脉根部连续切片;以HE染色观察形态学变化,免疫组织化学法检测主动脉壁内C反应蛋白和组织因子的表达水平,以Image Pro Plus6.0软件进行图像分析。结果南蛇藤素干预组主动脉粥样硬化斑块面积明显小于对照组,分别为4947±1277μm2和8403±2535μm2(P<0.05);南蛇藤素组主动脉粥样斑块面积/血管壁面积比值明显小于对照组(P<0.05);南蛇藤素组动脉壁C反应蛋白表达水平较对照组明显减少,平均光密度值分别为0.0152±0.0052与0.0256±0.0026(P<0.05);动脉粥样硬化斑块内组织因子表达水平较对照组明显减少,平均光密度值分别为0.0326±0.0132与0.0763±0.0347(P<0.05)。结论南蛇藤素可能通过抑制载脂蛋白E基因敲除小鼠炎症反应和动脉壁中C反应蛋白的表达而发挥抗动脉粥样的作用;还可能通过减少粥样斑块中组织因子的产生,而进一步起到稳定动脉粥样硬化斑块的作用。Aim To investigate the effects of celastrol on the expression of C-reactive protein and tissue factor in the aorta of ApoE gene knockout mice with earlier atherosclerosis. Methods 8-week old male ApoE gene knockout mice were divided randomly into control group and celastrol treatment group （n = 6 in each group）, 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）. HE staining of root aorta were used to observe the histomorphological change and measure the size of atherosclerotic plaque,The expression of C-reactive protein and tissue factor were detected by immunological histochemical method. Results The area of lipid plaque in the mice treated with celastrol was significantly smaller than that of the control （P〈0.05）. The value of plaque area/aorta cross section area was also significantly less than that of the control（P〈0.05）. The expression of C-reactive protein in the aortic wall and tissue factor in the atherosclerotic plaque were significantly lower in celastrol group compared with the DMSO control group （P〈0.01 and P〈0.05, respectively）. Conclusions Celastrol may reduce the formation of atherosclerotic lesions by inhibiting inflammation and promote the stability of atherosclerotic plaque by reducing the TF production.

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 C反应蛋白 组织因子 炎症 

分 类 号：R363[医药卫生—病理学]