中国药物警戒2024,Vol.21Issue(7) :781-786.DOI:10.19803/j.1672-8629.20240204

MCOLN1通过调控溶酶体自噬改善动脉粥样硬化的机制研究

MCOLN1 ameliorates atherosclerosis by regulating lysosomal autophagy

袁喆歆 王文庆 黄一凡 张荣臻 汤煜程 张凌韩 张海莹 刘艳
中国药物警戒2024,Vol.21Issue(7) :781-786.DOI:10.19803/j.1672-8629.20240204

MCOLN1通过调控溶酶体自噬改善动脉粥样硬化的机制研究

MCOLN1 ameliorates atherosclerosis by regulating lysosomal autophagy

袁喆歆 1王文庆 1黄一凡 1张荣臻 1汤煜程 1张凌韩 1张海莹 1刘艳1
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作者信息

  • 1. 海南医科大学药学院,海南省热带药用植物研发重点实验室,海南海口 571199
  • 折叠

摘要

目的 评估瞬时受体电位黏蛋白1(MCOLN1)在动脉粥样硬化小鼠主动脉斑块形成中的作用,并探究其机制.方法 将野生型C57BL/6和ApoE-/-小鼠分为4组:对照组、模型组、MCOLN1过表达组和过表达阴性对照组.以高脂饮食喂养建立动脉粥样硬化模型.油红O和苏木精-伊红(HE)染色评估主动脉组织病理学变化;Western blot和免疫荧光染色检测相关蛋白及自噬标记因子表达,全面评估MCOLN1表达对巨噬细胞自噬和动脉粥样硬化发生发展的影响.结果 过表达MCOLN1可减少主动脉脂质堆积,抑制斑块形成,减轻动脉粥样硬化发展;MCOLN1改善溶酶体功能,促进巨噬细胞自噬,抑制细胞泡沫化.结论 MCOLN1通过促进巨噬细胞自噬减缓动脉粥样硬化进展,可为预防及治疗动脉粥样硬化提供新的药物靶点.

Abstract

Objective To assess the role of transient receptor potential channel mucolipin 1(MCOLN1)in the formation of aortic plaque in atherosclerotic mice and investigate the mechanism.Methods Wild-type C57BL/6 and ApoE-/-mice were divided into four groups:control,model,MCOLN1 overexpression,and overexpression negative control groups.An atherosclerosis model was established by feeding the mice with a high-fat diet.Oil red O and hematoxylin-eosin(HE)staining were used to determine the histopathological changes of the aorta.Western blot and immunofluorescence staining were used to detect the expressions of related proteins and autophagy markers,and evaluate the effect of MCOLN1 expressions on macrophage autophagy and atherosclerosis.Results Overexpression of MCOLN1 reduced aortic lipid accumulation,inhibited plaque formation,and attenuated the development of atherosclerosis.MCOLN1 improved lysosomal function,promoted macrophage autophagy,and inhibited cellular foaminess.Conclusion MCOLN1 has been found to decelerate the progression of atherosclerosis by promoting macrophage autophagy,which provides new potential drug targets for the prevention and treatment of atherosclerosis.

关键词

动脉粥样硬化/瞬时受体电位黏蛋白1/巨噬细胞/自噬/溶酶体/ApoE-/-小鼠

Key words

atherosclerosis/MCOLN1/macrophage/autophagy/lysosome/ApoE-/-mice

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基金项目

海南省自然科学基金资助项目(821QN0892)

海南医学院2022年研究生创新科研课题项目(HYYB2022A06)

海南医学院2022年大学生创新创业训练计划项目(X202211810020)

出版年

2024
中国药物警戒
国家药品监督管理局药品评价中心(国家药品不良反应监测中心)

中国药物警戒

CSTPCD
影响因子:1.105
ISSN:1672-8629
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