| KATP通道Kir6.2亚基E23K多态性对阿霉素损伤大鼠心肌细胞结构及自噬的影响 |
| 投稿时间：2016-12-07 修订日期：2016-12-19 点此下载全文 |
| 引用本文：袁文慧,万军,刘剑芳,王梦龙,叶晶,徐瑶,姜慧敏,王震.KATP通道Kir6.2亚基E23K多态性对阿霉素损伤大鼠心肌细胞结构及自噬的影响[J].医学研究杂志,2017,46(6):20-24 |
| DOI：
10.11969/j.issn.1673-548X.2017.06.006 |
| 摘要点击次数: 1153 |
| 全文下载次数: 765 |
|
| 基金项目:国家自然科学基金资助项目（81170208） |
|
| 中文摘要:目的 构建携带KATP通道Kir6.2亚基E23K多态性的大鼠模型，给予阿霉素损伤，探讨KATP通道Kir6.2亚基E23K多态性对于阿霉素损伤的心肌，心肌结构、功能及细胞自噬的影响。方法 利用定点突变的方法获得含有Kir6.2 KK基因型的大鼠并进行基因鉴定。将大鼠随机分为4组，即A组（WT+Saline组，SD大鼠+生理盐水）、B组（E23K+Saline组，Kir6.2 KK大鼠+生理盐水）、C组（WT+DOX组，SD大鼠+阿霉素）、D组（E23K+DOX组，Kir6.2 KK大鼠+阿霉素）。采用腹腔注射阿霉素的方法构建阿霉素损伤大鼠模型，对照组腹腔注射等体积的生理盐水。应用心脏彩超进行阿霉素损伤心肌病模型的鉴定及心脏结构和功能的评价（每组8只）。分别通过HE染色及天狼星红染色心肌组织切片，测量心肌细胞面积及心肌纤维化比例，并通过PCR方法检测纤维化相关标志物CTGF、TGF-β mRNA的表达。通过Western blot法技术测定心肌细胞自噬水平。结果 超声结果显示，阿霉素损伤的大鼠相比于盐水组存在明显的心肌重构及功能损伤（P<0.01），且E23K组变化较WT组更明显（P<0.01）。病理及纤维化相关标志物mRNA表达显示，阿霉素损伤的大鼠心肌纤维化程度明显加重（P<0.01），且E23K组纤维化程度较WT组更严重（P<0.01）；自噬相关蛋白表达量检测显示，阿霉素损伤的大鼠，自噬相关蛋白表达量显著增加（P<0.01），且E23K组明显高于WT组（P<0.01）。结论 在阿霉素损伤模型中，Kir6.2亚基E23K多态性对大鼠心脏结构、功能、纤维化程度及自噬表达均有显著影响。 |
| 中文关键词:心肌 E23K多态性 阿霉素 纤维化 自噬 |
| |
| Effect of ATP Sensitive Potassium Channel Kir 6.2 E23K Polymorphism on DOX Myocardial Injury Cardiac Structure and Autophagy in Rats |
|
|
| Abstract:Objective To construct a KATP channel Kir6.2 subunit of E23K polymorphism of rat model of DOX injury, and explore the KATP channel Kir6.2 subunit of E23K polymorphism of DOX myocardial injury and cardiac structure, function and influence of Autophagy. Methods (1) Using site-directed mutagenesis methods,we gotrats containing Kir6.2 KK rat gene identification and genotype. The rats were randomly divided into 4 groups:A:WT+ Saline group (SD rat + saline); B:E23K+ Saline group (Kir6.2 KK rat + saline); C:WT-DOX group (SD rat + Doxorubicin); D:E23K-DOX group (Kir6.2 KK rat + Doxorubicin). Intraperitoneal injection of DOX in the model for rats spread disease, Intraperitoneal injection of an equal volume of saline control group.(2) Cardiac ultrasound is used to spread disease modeling, identification and evaluation of cardiac structure and function (8 rats in each group). Through HE and Sirius red staining tissue slices, we measured area of myocardial cells and ratio of myocardial fibrosis. And PCR methods for detection of fibrosis index,such as CTGF,TGF-β. Through Western blot technology,we measured levels of Autophagy. Results Ultrasound results showed that compared to group DOX rats with heart damage had significant cardiac remodeling and dysfunction(P<0.01),and compared with WT group E23K group,had more obvious changes (P<0.01). Pathology and fibrosis index of PCR results show that myocardial fibrosis was significantly increased in rat DOX injuried(P<0.01). Autophagy-related protein expression in testing showed that rats with DOX damage, Autophagy-related protein expression was significantly increased(P<0.01) in E23K group than in the WT group(P<0.01). Conclusion In the dilated Cardiomyopathy model which was constructed by DOX,the Kir 6.2 E23K polymorphism has a significant impact on cardiac structure,function,the level of fibrosis,and autophagy. |
| keywords:Cardiology E23K polymorphism Doxorubicin Fibrosis Autophagy |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
|
|
