KCN基因对小鼠脂代谢的影响及其机制初探

doi:10.3969/j.issn.1006-7795.2017.02.004

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (2): 161-166.doi: 10.3969/j.issn.1006-7795.2017.02.004

KCN基因对小鼠脂代谢的影响及其机制初探

刘敬怡^1,2, 卢晶^1,2, 杨金奎^1,2

1. 首都医科大学附属北京同仁医院内分泌科, 北京 100730;
2. 糖尿病防治研究北京市重点实验室, 北京 100730

收稿日期:2017-01-20 出版日期:2017-03-21 发布日期:2017-04-17
通讯作者: 杨金奎,E-mail:jinkui.yang@gmail.com E-mail:jinkui.yang@gmail.com
基金资助:
国家自然科学基金（81370946，81400824，81300726），北京市自然科学基金（7131005）

Effect of KCN potassium channel gene on lipid metabolism in mice

Liu Jingyi^1,2, Lu Jing^1,2, Yang Jinkui^1,2

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
2. Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China

Received:2017-01-20 Online:2017-03-21 Published:2017-04-17
Supported by:
This study was supported by National Natural Science Foundation of China (81370946, 81400824, 81300726), Natural Science Foundation of Beijing (7131005)

摘要/Abstract

摘要： 目的研究钾离子电压门控通道（potassium voltage-gated channel，KCN）基因对小鼠脂代谢的影响及其相关信号通路，为治疗糖尿病的脂肪异常提供新的治疗靶点。方法采用KCN基因敲除的小鼠模型及对照C57BL/6野生小鼠动物模型，检测三酰甘油、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇等脂代谢相关指标。HE染色观察小鼠肝脏组织脂肪变。Western blotting法测定小鼠肝脏组织腺苷酸激活蛋白激酶[adenosine 5'-monophosphate（AMP）-activated protein kinase，AMPK]通路相关蛋白的表达。结果 KCN基因敲除小鼠较野生型对照小鼠血清中三酰甘油、总胆固醇和低密度脂蛋白胆固醇浓度均明显增高，差异有统计学意义（P<0.05）高密度脂蛋白明显降低，肝脏HE染色显示基因敲除小鼠肝脏内脂滴的数目和体积均与野生型有明显差异，Western blotting结果显示KCN基因敲除小鼠肝脏组织中磷酸化蛋白激酶B（phosphate-protein kinase B，Phos-AKT）、磷酸化乙酰辅酶A羧化酶（phosphate-acetyl CoA carboxylase，Phos-ACC）、phos-AMPK浓度均较正常对照组小鼠表达量降低，phos-ACCα水平较正常对照组小鼠明显增高差异有统计学意义（P<0.05）。结论 KCN基因对小鼠血脂代谢有保护作用，其作用机制与AMPK的脂肪酸氧化有关。

关键词: 钾离子电压门控通道(potassium voltage-gated channel, KCN), 脂代谢, AMPK通络

Abstract: Objective To study the effect of potassium channel gene (KCN) on lipid metabolism in mice and its related signal pathway and to provide a new therapeutic target for dyslipidemia in diabetes. Methods Our group constructed KCN channel knock-out mouse model. In this study, KCN channel knock-out mice and control C57BL/6 mice will be examined. We will detect total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein in their serum, the protein level of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway from rat's tissue was detected by western blot and the level of hepatic steatosis will be observed by HE staining. Results The serum levels of total cholesterol, triglyceride and low-density lipoprotein in KCN gene knock-out mouse were all significantly higher than those in controls, and high-density lipoprotein is lower than control (P<0.05). The results of Western blotting showed that phosphate-protein kinase B (Phos-AKT) and phos-AMPK levels in liver tissue of KCN gene knockout mice were lower than those in normal control group, and phosphate-acetyl CoA carboxylase (phos-ACCα) level was significantly higher (P<0.05). Conclusion KCN channel influences lipid metabolism in mice by classical fatty acid oxidation AMPK pathway.

Key words: potassium voltage-gated channel, lipid metabolism, adenosine 5'-monophosphate (AMP)-activated protein kinase pathway

中图分类号:

R589.2

刘敬怡, 卢晶, 杨金奎. KCN基因对小鼠脂代谢的影响及其机制初探[J]. 首都医科大学学报, 2017, 38(2): 161-166.

Liu Jingyi, Lu Jing, Yang Jinkui. Effect of KCN potassium channel gene on lipid metabolism in mice[J]. Journal of Capital Medical University, 2017, 38(2): 161-166.

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KCN基因对小鼠脂代谢的影响及其机制初探

Effect of KCN potassium channel gene on lipid metabolism in mice

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