RESUMO
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 expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.