解偶联蛋白2对高糖诱导心肌线粒体损伤与细胞凋亡的调节作用  

Effect of uncoupling protein 2 on high-glucose induced mitochondrial damage and apoptosis of cardiomyocytes

作　　者：刁佳宇[1] 魏瑾[1] 闫蕊[1] 林琳[1] 李红[1] 

机构地区：[1]西安交通大学第二附属医院心内科,710004

出　　处：《中华医学杂志》2016年第31期2493-2497,共5页National Medical Journal of China

基　　金：国家自然科学基金（81170209）;陕西省自然科学基金（2015JM8431）

摘　　要：目的观察解偶联蛋白2（UCP2）在高糖干预下的心肌细胞中的表达水平，以及对线粒体功能与细胞凋亡的影响。方法将同期培养的ACl5人心肌细胞按随机数方法随机分为正常糖对照组、高糖组、高糖＋UCP2siRNA组、高糖＋阴性对照siRNA组，分别测定各组细胞中UCP2表达水平、琥珀酸脱氢酶（SDH）活性、三磷酸腺苷（ATP）含量、细胞内活性氧水平、细胞凋亡率、caspase-3活性与细胞活力的变化。结果高糖干预使心肌细胞活性氧生成增多、SDH活性下降与ATP生成减少，并引起细胞凋亡增加、casapse-3活性增强、细胞活力减弱，同时UCP2表达水平升高；抑制心肌细胞内UCP2表达则使高糖诱导的心肌细胞内活性氧生成（37．96±1．08比27．68±0．60，P〈0．05）进一步增多，细胞凋亡[（25．68±0．78）％比（17．80±0．99）％，P〈0．05]、caspase-3活化[（2．714-0．13）％比（2．14±0．28）％，P〈0．05]及细胞失活（0．74．4-0．04比0．62±0．03，P〈0．05）进一步加剧，而对SDH活性、ATP生成无明显影响。结论高糖诱导下的心肌细胞内UCP2表达上调可能是对线粒体损伤的反馈性保护机制，UCP2可能抑制高糖诱导的心肌细胞凋亡。Objective To observe the expression of uncoupling protein （UCP2） and its effect on modulation of mitochondrial function and apoptosis of cardiomyoeytes exposed to high-glucose. Methods AC16 eardiomyoetyes were randomly divided into normal-glucose group （ NG）, high-glucose group （ HG）, HG ± UCP2 siRNA group and HG ± negative control siRNA group. The expression of UCP2, succinodehydrogenase （SDH） activity, ATP content, reactive oxygen species （ROS） generation, cell apoptotic rate, caspase-3 activity and cell viability were detected. Results Compared with the cardiomyoeytes in NG group, the ROS production, apoptotic rate and caspase-3 activity were significantly increased in HG group, accompanying with the decreases in SDH activity, ATP content and cell viability. The expression of UCP2 was increased in HG group. Furthermore, UCP2 siRNA inhibited the expression of UCP2 and aggravated high-glucose induced the ROS production （ 37.96 ± 1.08 vs 27.68 ± 0. 60, P 〈 0. 05 ）, cell apoptosis （ （25.68 ± 0. 78 ） % vs （ 17.80 ± 0. 99 ） %, P 〈 0. 05 ）, caspase-3 activity （ （2. 71 ± 0. 13 ） % vs （2. 14 ± 0. 28 ） %, P 〈 0. 05 ） and cell inactivation （0. 74 ± 0. 04 vs 0. 62 ± 0.03, P 〈 0. 05）, but had no impact on SDH activity and ATP content in cardiomyocytes. Conclusion The up- regulation of UCP2 expression in cardiomyocytes, induced by high-glucose, maybe a protective mechanism for the mitochondrial damage, and UCP2 may inhibit high-glucose induced cardiomyocytes apoptosis.

关 键 词：解耦联蛋白2 心肌细胞 线粒体 细胞凋亡 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]