FOXA2改善肝内胆汁淤积伴高脂血症小鼠肝脏功能和血脂水平

被引：4

作者：

张梦洁 ^{[1
]}

杨洋 ^{[2
]}

陈慧 ^{[2
]}

陈思聪 ^{[2
]}

翟华立 ^{[2
]}

杨晓明 ^{[1
,2
]}

于淼 ^{[1
,2
]}

焦轶 ^{[1
]}

机构：

[1] 安徽医科大学基础医学院人体解剖学教研室

[2] 军事科学院军事医学研究院生命组学研究所蛋白质组学国家重点实验室

来源：

中国药理学通报 | 2021年 / 37卷 / 11期

基金：

北京市自然科学基金;

关键词：

叉头框蛋白A2; 胆汁淤积; 胆固醇; 高脂血症; 脂质代谢; 胆汁酸;

D O I：

暂无

中图分类号：

R589.2 [脂肪代谢障碍]; R575 [肝及胆疾病];

学科分类号：

100201 [内科学];

摘要：

目的研究叉头框蛋白A2(forkhead box A2,FOXA2)对肝内胆汁淤积伴高脂血症小鼠肝脏功能和血脂水平的调节作用。方法通过饲喂高胆固醇/胆酸饲料(cholic acid diet, CAD)构建小鼠模型,尾静脉高压注射法向小鼠肝脏内转染FOXA2质粒,使肝细胞过表达FOXA2蛋白。全自动血生化分析仪检测小鼠血清转氨酶、甘油三酯、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和胆汁酸水平,比色法检测肝脏内胆固醇水平,ELISA法检测肝脏胆汁酸水平。Western blot检测肝脏FOXA2的表达,RT-PCR检测胆汁酸代谢相关基因mRNA表达情况。HE、油红染色观察肝脏组织结构及脂质积累情况。结果随着CAD饲喂时间延长,小鼠体质量不断下降,胆囊明显增大(P<0.01),转氨酶水平升高、血清胆固醇和低密度脂蛋白胆固醇明显升高(P<0.01),肝脏组织结构受损,肝脏胆固醇、胆汁酸水平升高(P<0.01),脂质累积严重。过表达FOXA2可通过调节肝脏胆汁酸代谢基因明显改善CAD饲喂小鼠肝功能和血脂异常,降低肝脏胆汁酸水平(P<0.01)和肝脏脂质积累。结论 FOXA2改善肝内胆汁淤积伴高脂血症小鼠肝脏功能和血脂水平。

引用

页码：1593 / 1599

页数：7

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