摘要
目的观察南蛇藤素对ApoE基因敲除小鼠在动脉粥样硬化斑块形成的早期阶段主动脉壁中巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响。方法8周龄雄性ApoE基因敲除小鼠12只,按随机数字表法分为南蛇藤素干预组和对照组,每组6只,均给予高脂饮食饲养8周,在高脂饲养的后4周,分别予以2mg.kg-1.d-1南蛇藤素和相当剂量的溶剂二甲基亚砜(DMSO)腹腔注射,每日1次,连续用药4周;小鼠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,测定ApoE基因敲除小鼠主动脉根部粥样斑块面积,同时采用免疫组化方法观察主动脉壁MIF和MMP-9蛋白表达的强度。结果图像分析测量结果显示对照组形成了早期斑块;南蛇藤素干预组斑块面积较对照组明显减小(P<0.01),斑块面积/动脉壁横切面积也明显降低(P<0.01);南蛇藤素干预组与对照组比较,MIF、MMP-9的表达均明显降低(P<0.01)。结论南蛇藤素可能通过下调ApoE基因敲除小鼠主动脉壁MIF、MMP-9表达,发挥一定的抗动脉粥样硬化作用。
Objective To investigate the effects of celastrol on the expressions of macrophage migration inhibitory factor （MIF） and matrix metalloproteinase-9 （MMP-9） in the aorta of apoE gene knockout mice with earlier atherosclerosis. Methods Eight-week-old ApoE gene knockout male 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^- 1· d^ - 1 ） by intraperitoneal injection for 4 weeks ; and 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 changes and measure the size of plaque in ApoE^-/- mice. The expressions of MIF and MMP-9 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 〈0.01 ）, and so was the plaque area/aorta cross section area （P 〈0.01 ）. The expression of MIF was significantly decreased in celastrol group compared with the control group （P 〈0.01 ） The expression of MMP-9 was also significantly decreased in celastrol group compared with the control group （ P 〈 0.01 ）. Conclusion Celastrol can inhibit the progress of atherosclerotic plaque in ApoE^-/- mice, which might be relative to its inhibitory effects on the expression of MIF and MMP-9 in the aorta.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第9期827-830,共4页
Journal of Third Military Medical University
