摘要： 目的 探讨ASB14在心力衰竭小鼠中的作用及与泛素化介导的线粒体自噬的关系。方法 C57BL/6小鼠尾静脉注射ASB14-siRNA，3周后利用缩窄胸主动脉方法构建心力衰竭小鼠模型，评估小鼠心功能和病理组织学改变；采用实时PCR、Western blotting分别检测各组心脏ASB14 mRNA及蛋白、PINK1、Parkin及Mfn2、TIM23、COXIV、LC-3B及p62的表达。结果 经ASB14-siRNA注射小鼠心功能明显改善，心肌损伤减轻，PINK1及Parkin表达升高，Mfn2表达降低；而线粒体自噬标志蛋白TIM23、COXIV及p62蛋白明显降低，LC3II/LC3I的比例升高，与模型组相比，差异有统计学意义（P < 0.05）。结论 ASB14可能是通过调控泛素化降解，增加线粒体自噬，来改善小鼠心力衰竭的。

ASB14通过调控泛素化介导的线粒体自噬改善小鼠心力衰竭

王澈, 杨宏辉, 李庆民, 杜秋波, 朱利杰, 李清曼, 张彩丽

河南省人民医院, 阜外华中心血管病医院, 郑州大学人民医院心内科, 郑州 450000

收稿日期:2019-04-01出版日期:2020-07-30发布日期:2020-07-02
通讯作者:杨宏辉E-mail:18703710099@163.com
作者简介:王澈(1983-),女,主治医师,硕士.
基金资助:河南省重点科技攻关项目（112102310221）


关键词: ASB14, 泛素化, 线粒体自噬, 心力衰竭
Abstract: Objective To investigate the role of ASB14 in ubiquitination-mediated mitochondrial autophagy in mice with heart failure. Methods C57BL/6 mice were injected with ASB14-siRNA via the tail vein. Three weeks later,a mouse model of heart failure was established by narrowing the thoracic aorta. The heart function and histopathological changes of the mice were evaluated. ASB14 and PINK1 levels were detected in each group;Parkin,Mfn2,TIM23,COXIV,LC-3B,and p62 expression levels were also measured. Results In mice injected with ASB14-siRNA,heart function improved significantly,myocardial damage was reduced,PINK1 and Parkin expression increased,Mfn2 expression decreased,the expression of the mitochondrial autophagy marker proteins TIM23,COXIV,and p62 decreased,and the LC3II/LC3I ratio increased. Compared with the model group,these differences were statistically significant (P < 0.05). Conclusion ASB14 may ameliorate heart failure in mice by regulating ubiquitin degradation and increasing mitochondrial autophagy.
Key words: ASB14, ubiquitination, mitochondrial autophagy, heart failure
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