miRNA-208a-3p过表达致慢性心衰大鼠心肌细胞线粒体钙超载和功能障碍的机制研究
Research on mechanism of miRNA-208a-3p overexpression leading to mitochondrial calcium overload and dysfunction in cardiomyocytes of chronic heart failure rats
马丽娟 1周祁娜 2张健 3朱嘉俊 3王宝珠 3段明军 4李发鹏3
作者信息
- 1. 新疆医科大学第一附属医院门诊部,乌鲁木齐 830054
- 2. Queensland Health,Redland Hospital,Canaipa/HDU Ward.Australia,QLD,Brisbane,4116
- 3. 新疆医科大学第一附属医院心血管病中心心脏重症监护室,乌鲁木齐 830054
- 4. 新疆医科大学实验室与设备管理处动物实验中心,乌鲁木齐 830017
- 折叠
摘要
目的 观察miRNA-208a-3p在慢性心力衰竭大鼠心肌中的表达水平,探讨其在线粒体钙稳态和线粒体功能方面的调节机制.方法 35只健康SD大鼠,随机分为模型组(n=20)和对照组(n=15),模型组采用腹主动脉直径缩窄法建立慢性心衰模型,对照组行假手术.通过心功能和组织病理学检测评价模型,测定心肌miR-208a-3p表达,心肌线粒体去乙酰化酶3(SIRT3)蛋白和NADH脱氢酶亚基1(ND1)蛋白表达、线粒体Ca2+水平、心肌细胞活性氧(ROS)生成.结果 模型组大鼠心肌miR-208a-3p表达水平显著高于对照组(P＜0.05),SIRT3蛋白表达显著低于对照组(P＜0.001),且miR-208a-3p与SIRT3表达呈显著负相关;模型组ND1蛋白表达显著低于对照组(P＜0.05),且ND1与SIRT3表达呈显著正相关;模型组心肌细胞线粒体内Ca2+水平显著高于对照组(P＜0.05),心肌细胞ROS生成也显著高于对照组(P＜0.05).结论 慢性心衰心肌组织miR-208a-3p过度表达与SIRT3/ND1活性降低相关,抑制线粒体呼吸链活性,此外,心肌细胞出现线粒体钙超载和ROS生成增加,进一步加剧线粒体呼吸功能障碍,是慢性心衰线粒体功能障碍的重要机制.
Abstract
Objective To explore the mechanism of miRNA-208a-3p promoting the occurrence and develop-ment of chronic heart failure by regulating mitochondrial calcium homeostasis and mitochondrial function.Methods 35 healthy SD rats were randomly divided into model group(n=20)and control group(n=15).The abdominal aorta diameter constriction method was used to establish a chronic heart failure model in the model group,while the control group underwent sham surgery.The model was evaluated via cardiac function and histopathology.The measurement included mitochondrial miR-208a-3p expression,mito-chondrial sirtuin 3(SIRT3)expression and NADH dehydrogenase 1(ND1)expression,mitochondrial Ca2+level,cardiomyocyte ROS production.Results The expression level of miR-208a-3p in the rat heart failure model group was significantly higher than that in the control group(P＜0.05);The expression level of SIRT3 protein in the model group was significantly lower than the control group(P＜0.001),and there was an significant negative correlation between the level of miR-208a-3p and SIRT3 protein.The ex-pression level of ND1 protein in the model group was significantly lower than that of the control group(P＜0.05),and there was a significant positive correlation between the level of ND1 and SIRT3 protein.The mitochondrial Ca2+level of left ventricular cardiomyocytes in the model group was significantly higher than that in the control group(P＜0.05).The ROS generation of cardiomyocytes in the model group was sig-nificantly higher than that in the control group(P＜0.05).Conclusion Over-expression of miR-208a-3p in chronic heart failure myocardial tissue is associated with decreased SIRT3/ND1 activity,which inhibits mitochondrial respiratory chain activity.In addition,myocardial cells exhibit mitochondrial calcium over-load and increased ROS generation,further exacerbating mitochondrial respiratory dysfunction,which is an important mechanism of mitochondrial dysfunction in chronic heart failure.
关键词
慢性心衰/心肌细胞线粒体/钙超载/microRNA/线粒体去乙酰化酶3Key words
chronic heart failure/mitochondria/calcium overload/microRNA/SIRT3引用本文复制引用
基金项目
新疆维吾尔自治区自然科学基金面上项目(2021D01C314)
出版年
2024
NETL
NSTL
万方数据