MCOLN1通过调控溶酶体自噬改善动脉粥样硬化的机制研究

doi:10.19803/j.1672-8629.20240204

中国药物警戒 ›› 2024, Vol. 21 ›› Issue (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

袁喆歆, 王文庆^Δ, 黄一凡, 张荣臻, 汤煜程, 张凌韩, 张海莹^#, 刘艳^*

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

收稿日期:2024-03-26 出版日期:2024-07-15 发布日期:2024-07-31
通讯作者: ^* 刘艳,女,博士,教授·博导,心血管疾病。E-mail: liuyan_gyp@163.com;^#为共同通信作者。
作者简介:袁喆歆,男,硕士,药理学。^Δ为并列第一作者。
基金资助:
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）

MCOLN1 ameliorates atherosclerosis by regulating lysosomal autophagy

YUAN Zhexin, WANG Wenqing^Δ, HUANG Yifan, ZHANG Rongzhen, TANG Yucheng, ZHANG Linghan, ZHANG Haiying^#, LIU Yan^*

School of Pharmacy, Hainan Medical University/Key Laboratory of Research and Development of Tropical Medicinal Plants, Hainan Province, Haikou Hainan 571199, China

Received:2024-03-26 Online:2024-07-15 Published:2024-07-31

摘要/Abstract

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。

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

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.

Key words: atherosclerosis, MCOLN1, macrophage, autophagy, lysosome, ApoE^-/-mice

中图分类号:

R972

袁喆歆, 王文庆, 黄一凡, 张荣臻, 汤煜程, 张凌韩, 张海莹, 刘艳. MCOLN1通过调控溶酶体自噬改善动脉粥样硬化的机制研究[J]. 中国药物警戒, 2024, 21(7): 781-786.

YUAN Zhexin, WANG Wenqing, HUANG Yifan, ZHANG Rongzhen, TANG Yucheng, ZHANG Linghan, ZHANG Haiying, LIU Yan. MCOLN1 ameliorates atherosclerosis by regulating lysosomal autophagy[J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 781-786.

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https://zgywjj.magtechjournal.com/CN/Y2024/V21/I7/781

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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

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