FGF-21通过上调肝脏LDL受体的表达降低血浆中LDL水平  

FGF-21 decreases plasma LDL by upregulating liver LDLR expression

作　　者：于艺雪[1] 任桂萍[1] 王文飞[1] 王菁[1] 孙国鹏[1] 张巧[1] 刘铭瑶[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院生物制药教研室,黑龙江哈尔滨150030

出　　处：《中国药理学通报》2010年第6期798-802,共5页Chinese Pharmacological Bulletin

基　　金：黑龙江省科技厅攻关项目资助(No2006G0461-00);哈尔滨市科技创新人才发展计划资助(No2006RFXXS002);东北农业大学创新团队发展计划资助

摘　　要：目的成纤维细胞生长因子-21(FGF-21)可降低实验动物血浆中的低密度脂蛋白(LDL)的浓度,但其作用机制尚不清楚,本实验试图通过研究FGF-21对LDLR的调节作用揭示FGF-21调节血浆LDL浓度的机制。方法向谷氨酸钠(MSG)肥胖大鼠连续注射FGF-21蛋白40d后,检测其血浆中LDL的变化,并用荧光定量PCR的方法结合免疫荧光检测FGF-21对肝脏组织中LDLR mRNA及蛋白的影响。结果 MSG肥胖鼠经FGF-21处理,血浆内的LDL降低18%,其肝脏组织中LDLR mRNA含量提高9倍;HepG2细胞内的LDLR mRNA表达量随FGF-21处理时间增加而提高,且呈剂量依赖性;流式细胞仪检测显示,经FGF-21处理后HepG2细胞表面LDLR蛋白数量增加。结论 FGF-21通过增加肝细胞的LDLR表达量从而降低血浆中LDL浓度。Aim To investigate whether fibroblast growth factor-21 （FGF-21） has effects on liver low density lipoprotein receptor（LDLR）.Methods Obesity rat model was successfully established by injecting glutamic sodium （MSG）.The experimental rats were then treated with FGF-21 at 1 mg·kg-1·d^-1 for 40 days.The concentration of plasma low density lipoprotein （LDL） was detected.The changes of LDLR mRNA expression in HepG2 cells treated with FGF-21 were detected by real-time PCR,and the change of cell surface LDLR was assessed by flowcytometry.Results After FGF-21 treated,the concentration of LDL in obesity model rat plasma was decreased by 18%.The expression of LDLR mRNA was continuously increased in HepG2 cells treated with FGF-21,furthermore,the LDLR mRNA level was increased in a dose-dependent manner at the same time point.These changes were accompanied by increased expression of LDLR protein on HepG2 cell surface.Conclusion FGF-21 induces the expression of LDLR both in vivo and in vitro,and it decreases plasma LDL by upregulating liver LDLR expression.

关 键 词：成纤维细胞生长因子-21 肝脏 低密度脂蛋白 低密度脂蛋白受体 HEPG2细胞 谷氨酸钠 

分 类 号：R-332[医药卫生] R322.47