阿伐他汀对高胆固醇血症ApoE基因敲除小鼠肝脏骨桥蛋白表达的影响  

Effects of atorvastatin on expression of osteopontin in liver of the hypercholesterolemia ApoE gene knockout mice

作　　者：刘超[1] 江志奎[1,2] 程筱雯[1] 肖林林[1] 朱华庆[1] 左莉[1] 张素梅[1] 胡若磊[1] 陈孝宇[1] 周青[1] 汪渊[1] 

机构地区：[1]安徽医科大学分子生物学实验室、生物化学教研室和安徽省／省部共建教育部重要遗传病基因资源利用重点实验室,合肥230032 [2]安徽医科大学解放军临床学院(解放军第105医院),合肥230023

出　　处：《安徽医科大学学报》2008年第6期670-673,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30570750);安徽省自然科学基金(编号:070413079);南京军区医学科研基金(编号:07M034-A)

摘　　要：目的探讨阿伐他汀对高胆固醇血症ApoE基因敲除小鼠肝脏骨桥蛋白(OPN)表达的影响。方法18只4周龄ApoE基因敲除小鼠,随机分为正常组、高胆固醇组、高胆固醇+阿伐他汀组。高胆固醇+阿伐他汀组给予阿伐他汀5mg/(kg·d),12周后获取血和肝脏。分析血清胆固醇和低密度脂蛋白浓度。肝脏组织切片用于HE染色以观察肝脏组织学病变;应用免疫组化PV法检测肝脏组织中OPN的表达;从冰冻肝脏组织中提取蛋白,用Western blot方法检测OPN变化。结果阿伐他汀有显著降血清胆固醇和抑制肝脏的脂肪病变的作用;免疫组织化学和Western blot检测结果显示,高胆固醇+阿伐他汀组OPN表达比高胆固醇组显著降低(P<0.05)。结论阿伐他汀可降低高胆固醇血症ApoE基因敲除小鼠血清胆固醇浓度,抑制肝脂肪变性,下调OPN的表达。Objective To investigate the effects of atorvastatin on expression of osteopontin in liver of the hypercholesterolemia ApoE gene knockout mice. Methods 4-week-old ApoE knockout mice were randomly divided into normal group, high cholesterol group and high-cholesterol ＋ atorvastatin group. The mice with High-cholesterol were given atorvastatin 5 mg / （kg · d）. The blood and liver were obtained afterl2 weeks . Serum cholesterol and low density lipoprotein-cholesterol are analyzed. Liver specimens were for HE stain to observe liver organizational changes and for PV immunohistochemistry to detect OPN expression and distribution in liver of normal group, high - cholesterol group and high-cholesterol ＋ atorvastatin group. Protein extraction from frozen liver was for western blot to test the change of osteopontin expression in the three groups. Results Atorvastatin was significant in the role of lowering cholesterol and the inhibition of liver steatosis; Immunohistochemistry and Western blot test results show that high-cholesterol ＋ atorvastatin group was significant reduction of osteopontin expression than the high cholesterol group （P 〈 0. 05 ）. Conclusion Atorvastatin could inhibit the synthesis of cholesterol levels, inhibit liver steatosis and reduce osteopontin expression.

关 键 词：高胆固醇血症 小鼠 基因敲除 

分 类 号：R589.2[医药卫生—内分泌] R341[医药卫生—内科学]