罗格列酮对ApoE基因敲除小鼠动脉粥样硬化的影响

Rosiglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice

目的探讨罗格列酮对ApoE基因敲除小鼠主动脉粥样硬化病变的影响。方法32只6周龄ApoE基因敲除小鼠随机分为治疗组(18只)和对照组(14只),两组均饲喂普通饮食,治疗组给予罗格列酮17mg·kg-1·d-1,14周后获取静脉血和主动脉全长标本作生化和病理分析。主动脉根部1cm标本进行切片(横切面)HE染色,观察横切面动脉硬化病变的面积及组织学变化;免疫组化法半定量观察横切面斑块内TNFα和巨噬细胞的阳性率。其余大部分主动脉沿长轴剖开,苏丹Ⅳ染色,分析纵剖面斑块面积占主动脉的面积比。结果罗格列酮组脂纹病变数目显著多于对照组,但两组斑块总数目、纤维病变和粥样病变的数目无明显差异。横切面,主动脉根部的斑块面积与对照组相比,无明显改变。纵剖面,罗格列酮组斑块面积占纵剖面主动脉面积之比明显小于对照组。罗格列酮组斑块内炎性因子TNFα水平和巨噬细胞的含量明显减少。结论罗格列酮可能通过下调炎性因子TNFα的水平,减少斑块内巨噬细胞的数量,抑制动脉粥样硬化病变的发展。

ObjectiveTo study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice. MethodsThirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n=18) and control group (n=14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root(1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-α were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section. ResultsThe amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-α in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group. ConclusionRosiglitazone suppresses the expression of tumor necrosis factor-α, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.