川芎-赤芍药对干预心肌梗死合并动脉粥样硬化复合模型的circRNA/lncRNA表达谱研究  

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model

作　　者：袁蓉[1] 李梓涵 黄美雯 李芃琪 缪宇[1] 莫蕙 曾莉 鞠振宇 信琪琪 丛伟红[1] YUAN Rong;LI Zi-han;HUANG Mei-wen;LI Peng-qi;MIAO Yu;MO Hui;ZENG Li;JU Zhen-yu;XIN Qi-qi;CONG Wei-hong(Laboratory of Cardiovascular Diseases,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Macao University of Science and Technology,Macao 999078,China;Macao Health Bureau,Macao 999078,China;Institute of Aging and Regenerative Medicine,Jinan University,Guangzhou 510632,China)

机构地区：[1]中国中医科学院,西苑医院心血管病实验室,北京100091 [2]天津中医药大学,天津301617 [3]澳门科技大学,中国澳门999078 [4]澳门卫生局,中国澳门999078 [5]暨南大学衰老与再生医学研究院,广东广州510632

出　　处：《中国中药杂志》2023年第14期3890-3903,共14页China Journal of Chinese Materia Medica

基　　金：中国中医科学院科技创新工程项目(CI2021A00914);国家自然科学基金项目(82104680,82004193)。

摘　　要：探索川芎-赤芍药对(Chuanxiong-Chishao herb pair,CX-CS)对心肌梗死合并动脉粥样硬化(myocardial infarction-atherosclerosis,MI-AS)小鼠复合模型的干预作用,并探讨其对缺血心肌、主动脉组织环状RNA(circular RNA,circRNA)/长链非编码RNA(long non-coding RNA,lncRNA)表达谱的影响。将60只雄性ApoE-/-小鼠随机分为模型组,CX-CS高(7.8 g·kg^(-1))、中(3.9 g·kg^(-1))、低(1.95 g·kg^(-1))剂量组,阳性药组(美托洛尔26 mg·kg^(-1),辛伐他汀5.2 mg·kg^(-1)),每组12只。假手术组采用雄性C57BL/6J小鼠。模型组及药物干预组给予高脂喂养10周后进行冠状动脉前降支结扎术,术后继续给予高脂饲料2周,建立MI-AS模型。假手术组给予普通饲料喂养,手术时只穿线不接扎。药物干预组于高脂喂养第9周起给予CX-CS、阳性药灌胃4周,模型组和假手术组给予等体积生理盐水。给药结束后取CX-CS中剂量组、模型组、假手术组心脏和主动脉组织行全转录组测序。结果发现,CX-CS高、中剂量组小鼠心功能显著改善、心肌纤维化面积缩小,CX-CS中剂量组斑块面积显著减小。CX-CS处理可逆转复合模型中粥样硬化主动脉的circRNA_07227、circRNA_11464以及缺血心肌的circRNA_11505等circRNA的表达。主动脉CX-CS(ACC)组与主动脉模型(AM)组间的差异circRNA主要富集在脂质合成、代谢及转运、炎症、血管新生等过程。心脏CX-CS(HCC)组与模型(HM)组间差异circRNA主要富集在血管新生、血压调节等过程。CX-CS处理可逆转复合模型中粥样硬化主动脉的ENSMUST00000162209以及缺血心肌的TCONS_00002123等lncRNA表达变化。ACC组与AM组间的差异lncRNA主要富集在脂质代谢、血管新生、自噬、凋亡、铁死亡等过程。HCC组与HM组间差异lncRNA主要富集在血管新生、自噬、铁死亡等过程。综上,CX-CS可调控多种circRNA及lncRNA的表达,其干预冠心病的机制可能与调控缺血心肌血管新生、炎症以及AS主动脉的This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS)on a myocardial infarction-atherosclerosis(MI-AS)mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs)in ischemic myocardium and aorta.Sixty male ApoE~(-/-)mice were randomly assigned to a model group,high-,medium-,and low-dose CX-CS groups(7.8,3.9,and 1.95 g·kg^(-1)),and a positive drug group(metoprolol 26 mg·kg^(-1)and simvastatin 5.2 mg·kg^(-1)),with 12 mice in each group.Male C57BL/6J mice were assigned to the sham group.The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks,followed by anterior descending coronary artery ligation.After that,the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model.The mice in the sham group received normal feed,followed by sham surgery without coronary artery ligation.Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding,and those in the model group and the sham group received an equal volume of normal saline.Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group,the model group,and the sham group after administration.The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area,and the medium-dose CX-CS group showed significantly reduced plaque area.CX-CS treatment could reverse the expression of circRNA_07227 and circRNA_11464 in the aorta of AS model and circRNA expression(such as circRNA_11505)in the heart of the MI model.Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis,lipid metabolism,lipid transport,inflammation,and angiogenesis in the aorta,and in angiogenesis,blood pressure regulation,and other processes in the heart.CX-CS treatment could reverse the expre

关 键 词：冠心病 川芎-赤芍药对 心肌梗死 动脉粥样硬化 环状RNA 长链非编码RNA 

分 类 号：R285.5[医药卫生—中药学]