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第42卷第11期 南京医科大学学报(自然科学版)
2022年11月 Journal of Nanjing Medical University(Natural Sciences) ·1515 ·
·基础研究·
血浆外泌体通过微小RNA⁃25⁃3p对心肌纤维化影响的初步研究
顾寰宇,李姗姗,王 芹,姜 敏 ,王 春 *
*
南京大学医学院附属鼓楼医院老年科,江苏 南京 210008
[摘 要] 目的:初步明确血浆外泌体及其内容物微小RNA⁃25⁃3p(microRNA⁃25⁃3p,miR⁃25⁃3p)对心肌纤维化的影响。方法:
分别提取10只健康C57BL/6小鼠(对照组)和10只心肌梗死术后小鼠(心肌纤维化模型组)的血浆外泌体。利用电镜、纳米跟
踪颗粒分析、标志物蛋白检测鉴定外泌体;实时荧光定量PCR(real⁃time quantitative polymerase chain reaction,qPCR)和蛋白质
印迹(Western blot)检测两种外泌体对血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)诱导下的小鼠心脏成纤维细胞纤维化水平的影
响;qPCR检测两种外泌体内miR⁃25⁃3p的水平;Western blot和免疫荧光染色检测miR⁃25⁃3p模拟物和抑制物对心脏成纤维细
胞增殖和向肌成纤维细胞分化能力的影响。结果:对照组血浆外泌体可使Ang Ⅱ诱导增加的纤维化相关指标下调,而心肌纤
维化模型组外泌体则失去这一功能且其内miR⁃25⁃3p含量更高;miR⁃25⁃3p模拟物上调纤维化相关指标,而miR⁃25⁃3p抑制物
则表现相反作用。结论:健康小鼠血浆外泌体可改善心肌纤维化;血浆外泌体内的miR⁃25⁃3p上调可促进心肌纤维化发生。
[关键词] 心肌梗死;心肌纤维化;血浆外泌体;miR⁃25⁃3p
[中图分类号] R542.23 [文献标志码] A [文章编号] 1007⁃4368(2022)11⁃1515⁃08
doi:10.7655/NYDXBNS20221103
Preliminary study to the effect of plasma exosome on cardiac fibrosis via microRNA⁃25⁃3p
*
GU Huanyu,LI Shanshan,WANG Qin,JIANG Min ,WANG Chun *
Department of Geriatrics,Nanjing Drum Tower Hospital,the Affiliated Hospital of Medical School of Nanjing
University,Nanjing 210008,China
[Abstract] Objective:This study aims to preliminary investigate the effect of plasma exosome and the content microRNA⁃ 25⁃3p
(miR ⁃ 25 ⁃ 3p)on myocardial fibrosis. Methods:The plasma exosomes of 10 healthy C57BL/6 mice(control group)and 10 mice
underwent myocardial infarction surgery(cardiac fibrosis model group)were collected successively. The exosomes were identified by
electron microscopy,nano tracking particle analysis and detection of marker protein;qPCR and Western blot were used to investigate
effects of the two different exosomes on the fibrosis level of mouse cardiac fibroblasts stimulated by angiotensin Ⅱ(Ang Ⅱ);
expression of miR⁃25⁃3p in exosomes from two groups were detected by qPCR;Western blot and immunofluorescence staining were
used to present the effects of miR⁃25⁃3p mimic and inhibitor on differentiation and proliferation of cardiac fibroblasts. Results:The
plasma exosomes of healthy mice attenuated the increased fibrosis level induced by Ang Ⅱ,while the plasma exosomes of myocardial
fibrosis model mice lost this function and contained more miR⁃25⁃3p;miR⁃25⁃3p mimic promoted cardiac fibrosis,while miR⁃25⁃3p
inhibitor showed the opposite effect. Conclusion:Plasma exosome of health mice can protect myocardial fibrosis;the up⁃regulated miR⁃
25⁃3p in plasma exosome promotes cardiac fibrosis.
[Key words] myocardial infarction;cardiac fibrosis;plasma exosome;miR⁃25⁃3p
[J Nanjing Med Univ,2022,42(11):1515⁃1522]
心肌纤维化几乎是所有慢性心血管疾病进展
到心力衰竭的重要病理状态,伴纤维化疾病已占所
[基金项目] 国家自然科学青年基金(81900220);南京市卫
[1]
有疾病死亡率的45% 。临床尚无有效药物治愈纤
生科技发展专项资金项目计划(YKK19052)
维化,除了心脏磁共振,在临床也无有效安全的诊
∗
通信作者(Corresponding author),E ⁃ mail:wangchun@njglyy.
[2]
com;jmin1212@hotmail.com 断标志物 。心肌纤维化是在致病因素如炎症、高