成纤维细胞生长因子21对载脂蛋白E基因敲除小鼠动脉粥样硬化病变中内质网应激诱导的凋亡的影响  

Effect of Fibroblast Growth Factor-21 on Endoplasmic Reticulum Stress-induced Apoptosis in Aorta of Apolipoprotein E-Knockout Mice

作　　者：伍熙[1] 赵东晖[1] 范谦[1] 程姝娟[1] 张铭[1] 彭红玉[1] 柳景华[1] 

机构地区：[1]首都医科大学附属北京安贞医院北京市心肺血管疾病研究所,北京市100029

出　　处：《中国动脉硬化杂志》2014年第4期325-329,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81070227);北京市教育委员会科技计划面上项目(KM201110025019)

摘　　要：目的探讨成纤维细胞生长因子21(FGF-21)对载脂蛋白E基因敲除(ApoE-/-)小鼠主动脉中内质网应激诱导的凋亡的影响。方法将24只ApoE-/-小鼠随机分为动脉粥样硬化模型组(简称模型组)和FGF-21组(n=12),另选12只C57BL/6J小鼠作为正常对照组,三组小鼠都给予高胆固醇饮食4周,同时FGF-21组皮下给予FGF-21[0.1 mg/(kg·d)]4周,而模型组和正常对照组给予等量生理盐水。4周后处死小鼠进行主动脉病理学检测,观察斑块面积,采用放射免疫法检测血浆中FGF-21的水平,采用免疫组织化学染色和Western Blot检测主动脉成纤维细胞生长因子受体1(FGFR-1)的表达水平,采用Tunel染色检测主动脉斑块中的细胞凋亡水平,采用Western Blot检测主动脉中剪切后Caspase-12和C/EBP同源蛋白(CHOP)的表达水平。结果与正常对照组比较,模型组血浆中的FGF-21水平及主动脉中FGFR1蛋白表达显著升高(P<0.05),模型组主动脉根部斑块面积、细胞凋亡数量、剪切后Caspase-12及CHOP蛋白的表达水平增加(P<0.05);与模型组比较,FGF-21组主动脉根部斑块面积、细胞凋亡数量、剪切后Caspase-12及CHOP蛋白的表达水平减少(P<0.05)。结论 FGF-21可能通过抑制剪切后Caspase-12及CHOP相关促凋亡蛋白表达,抑制ApoE-/-小鼠主动脉斑块病变中细胞的凋亡及斑块进展。Aim To investigate the effects of fibroblast growth factor-21（ FGF-21） on endoplasmic reticulum stress-induced apoptosis in aorta of ApoE- /-mice. Methods Twenty-four male ApoE- /-mice and twelve male C57BL /6J mice were divided into three groups： Control group（ n = 12）,atherosclerosis group（ n = 12） maintained high fat diet with vehicle administration subcutaneously for 4 weeks,and FGF-21 treatment group（ n = 12） ： the same fat diet with FGF-21 administration subcutaneously[0. 1 mg /（ kg·d） ] for 4 weeks. At the end of the study,all mice were sacrificed to detect the plasma FGF-21 levels,histopathological changes and apoptotic rate in aorta,fibroblast growth factor receptor-1（ FGFR-1）,cleaved cysteinyl aspartate specific proteinase-12（ Caspase-12） and C / EBP homologous protein（ CHOP） expression of the aortas. Results Compared with control group,atherosclerosis group fed with a high-fat diet showed upregulated levels of FGF-21 in plasma and FGFR-1 protein expression in aorta,and the plaque area,apoptotic rate, cleaved Caspase-12 and CHOP protein expression in aortas were significantly increased（ P〈0. 05）. Compared with atherosclerosis group,FGF-21 group showed less plaque area,apoptotic rate,cleaved Caspase-12 and CHOP protein expression in aortas（ P〈0. 05）. Conclusion FGF-21 can inhibit apoptosis and atherosclerosis possibly by inhibiting expression of pro-apoptotic proteins like cleaved Caspase-12 and CHOP in atherosclerotic aorta of ApoE- /-mice.

关 键 词：成纤维细胞生长因子21 细胞凋亡 动脉粥样硬化 

分 类 号：R363[医药卫生—病理学]