| 李 静,常 盼,张 静,王西辉,王建榜,陈伟国,铁 茹,于 军,吴 娟.MiR-146a通过炎症参与小鼠糖尿病心肌病的机制研究[J].现代生物医学进展英文版,2020,(5):848-852. |
| MiR-146a通过炎症参与小鼠糖尿病心肌病的机制研究 |
| Mechanism of miR-146a Involved in Diabetic Cardiomyopathy in Mice Through Inflammation |
| Received:August 07, 2019 Revised:August 31, 2019 |
| DOI：10.13241/j.cnki.pmb.2020.05.010 |
| 中文关键词: miR-146a 炎症因子 糖尿病心肌病 |
| 英文关键词: MiR-146a Inflammatory factor Diabetic cardiomyopathy |
| 基金项目:国家自然科学基金项目（81870172）；陕西省科技厅重点项目（2018ZDXMSF-068）；陕西省科技厅一般项目（2018SF-129，2018SF-114） |
| Author Name | Affiliation | E-mail | | LI Jing | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | 8683268@qq.com | | CHANG Pan | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | ZHANG Jing | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | WANG Xi-hui | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | WANG Jian-bang | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | CHEN Wei-guo | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | TIE Ru | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | | | YU Jun | Laboratory of Clinical Center, Xi'an Medical International Center, Xi'an, Shaanxi, 710119, China | | | WU Juan | Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical College and Clinical Research Center of Cardiovascular Diseases, Xi'an, Shaanxi, 710038, China | |
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| 中文摘要: |
| 摘要 目的：探讨microRNA-146a (miR-146a)对小鼠糖尿病心肌病炎症的影响。方法：20只雄性C57BL/6小鼠随机分为对照组和糖尿病心肌模型组，模型组利用链脲佐菌素(STZ，50 mg/kg)腹腔注射建立糖尿病心肌病模型，对照组给予等体积枸橼酸钠缓冲液，建模成功后提取心脏组织RNA，利用qRT-PCR检测心肌组织中miR-146a和炎症因子白介素1β（IL-1β），白介素6（IL-6），单核趋化因子1(MCP-1)以及NF-κB/p65的mRNA 表达；依次分离原代心肌细胞，成纤维细胞和内皮细胞，给予高糖处理后，检测细胞中miR-146a，IL-1β，IL-6，MCP-1以及NF-κB/p65的mRNA 表达；内皮细胞转染miR-146a mimic或miR-146a inhibitor，观察炎症因子的表达情况。结果：糖尿病心肌病心肌组织中miR-146a水平较对照组降低（P＜0.05），炎症因子IL-1β，IL-6，MCP-1以及NF-κB/p65的mRNA表达高于对照组（P＜0.05）；与对照组相比，高糖分别处理原代心肌细胞和成纤维细胞后miR-146a表达未改变（P＞0.05），而高糖降低内皮细胞中miR-146a的表达（P＜0.05）；高糖增加内皮细胞炎症因子IL-1β，IL-6，MCP-1及NF-κB/p65的mRNA水平（P＜0.05）；内皮细胞转染miR-146a mimic后可阻止由于高糖所导致的内皮细胞中IL-1β，IL-6，MCP-1及NF-κB/p65的增加（P＜0.05），而转染miR-146a inhibitor后，可引起正常对照组细胞中炎症因子IL-1β，IL-6，MCP-1以及NF-κB/p65表达的增加（P＜0.05）。结论：糖尿病心肌病中miR-146a的降低以及炎症的增加，与内皮细胞受损相关，且可能通过miR-146a影响炎症因子的表达。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of microRNA-146a (miR-146a) on inflammation of diabetic cardiomyopathy in mice. Methods: Twenty male C57BL/6 mice were randomly divided into control group and diabetic myocardial model group, with 10 rats in each group. The model group was established by intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to establish a diabetic cardiomyopathy model. The control group was intraperitoneally injected with an equal volume of sodium citrate buffer. Cardiac tissue RNA was extracted. qRT-PCR was used to detect the mRNA expression of miR-146a and inflammatory factor interleukin-1β (IL-1β), interleukin-6 (IL-6), monocyte chemotactic factor 1 (MCP-1) and NF-κB/p65; then cardiomyocytes, fibroblasts and endothelial cells were sequentially isolated from mice, and treated with high glucose. The mRNA expressions of miR-146a, IL-1β, IL-6, MCP-1 and NF-κB/p65 were detected in the cells. The expression of inflammatory factors was observed by transfecting miR-146a mimic or miR-146a inhibitor into endothelial cells. Results: The level of miR-146a in myocardial tissue of diabetic cardiomyopathy was lower than that of the control group (P＜0.05), and the mRNA expression of inflammatory factors IL-1β, IL-6, MCP-1 and NF-κB/p65 was higher than that of the control group (P＜0.05). After treatment of cardiomyocytes and fibroblasts with high glucose, the expression of miR-146a was unchanged compared with the control group (P＞0.05), while high glucose decreased the expression of miR-146a in endothelial cells (P＜0.05). High glucose increased mRNA levels of endothelial cytokines IL-1β, IL-6, MCP-1 and NF-κB/p65 (P＜0.05). Then transfected with miR-146a mimic prevented high glucose induced the increase of IL-1β, IL-6, MCP-1 and NF-κB/p65 in endothelial cells (P＜0.05), and transfection of miR-146a inhibitor can cause inflammatory factor IL-1β, IL-6, MCP-1 and NF-κB/p65 expression increased in normal control cells (P＜0.05). Conclusion: The decrease of miR-146a and the increase of inflammation in diabetic cardiomyopathy are associated with endothelial cell damage, and these effects may be affect the expression of inflammatory factors through miR-146a. |
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