| 摘要: |
| 目的 研究核黄素对主动脉弓缩窄（TAC）手术诱导的小鼠病理性心肌肥厚和纤维化的作用，初步探究其与短链酰基辅酶A脱氢酶（SCAD）的关系。方法 C57BL/6小鼠随机分为4组（n＝10）：假手术＋生理盐水（NS）组、TAC＋NS组、假手术＋核黄素组、TAC＋核黄素组，各组小鼠手术前1周至手术后4周予NS或核黄素连续灌胃5周，核黄素灌胃剂量为20 mg·kg-1·d-1。手术后第5周检测各组小鼠尾动脉收缩压，超声心动图评价小鼠心脏结构功能，计算心脏体重比、心脏胫骨长比，观察小鼠心脏形态学变化，检测小鼠心肌肥厚标志物mRNA表达水平、心肌胶原表达水平、心肌SCAD表达水平及其酶活性，检测心肌SCAD的辅酶黄素腺嘌呤二核苷酸（FAD）含量、ATP及游离脂肪酸含量变化。结果 核黄素能改善TAC手术诱导的小鼠病理性心肌肥厚与纤维化，同时增加心肌FAD含量（P＜0.01），提高SCAD蛋白和mRNA的表达水平与SCAD酶活性（P均＜0.01），减少心肌游离脂肪酸含量（P＜0.01），增加心肌ATP含量（P＜0.01）。结论 核黄素对小鼠病理性心肌肥厚和纤维化有改善作用，这种作用可能通过提高心肌FAD含量、促进心肌SCAD表达、增强心肌脂肪酸β氧化、改善心肌能量代谢实现。 |
| 关键词: 核黄素 短链酰基辅酶A脱氢酶 能量代谢 病理性心肌肥厚 心肌纤维化 |
| DOI：10.16781/j.CN31-2187/R.20220475 |
| 投稿时间：2022-06-06修订日期：2022-10-25 |
| 基金项目:国家自然科学基金(81670239)，国家临床重点专科建设项目（临床药学），广东省自然科学基金（2020A1515010223），广东省普通高校重点领域专项（2021ZDZX2019），广东省高水平临床重点专科（临床药学）. |
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| Riboflavin ameliorates pathological myocardial hypertrophy and fibrosis in mice by activating short-chain acyl-CoA dehydrogenase |
| PENG Huan1，2,XU Qing-ping1，2,SU Yong-shao1，2,FENG Jing-yun1，2,QIN Xue1，2,ZHOU Si-gui1，2* |
(1. Department of Clinical Traditional Chinese Medicine, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China;
2. Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510699, Guangdong, China
*Corresponding author) |
| Abstract: |
| Objective To explore the effect of riboflavin on pathological myocardial hypertrophy and fibrosis in mice induced by transverse aortic constriction (TAC), and to preliminarily explore the relationship between this effect and short-chain acyl-CoA dehydrogenase (SCAD). Methods The C57BL/6 mice were randomly divided into 4 groups (n＝10): sham operation＋normal saline (NS) group (sham＋NS group), TAC＋NS group, sham＋riboflavin group, and TAC＋riboflavin group. The mice in each group were gavaged continuously for 5 weeks from 1 week before the operation to 4 weeks after the operation, and the gavage dose of riboflavin was 20 mg·kg-1·d-1. The systolic blood pressure of the tail artery of the mice in each group was detected at the 5th week after the operation, the cardiac structure and function of the mice were evaluated by echocardiography, the heart weight/body weight ratio and heart weight/tibia length ratio were calculated, and the morphological changes of mice hearts were observed; the mRNA expression levels of cardiac hypertrophy markers in mice, the expression levels of mouse myocardial collagen, and the expression and enzymatic activity of SCAD were detected, and the contents of coenzyme flavin adenine dinucleotide (FAD) in myocardial SCAD, adenosine triphosphate (ATP) and free fatty acid were detected. Results Riboflavin could improve TAC surgery-induced pathological myocardial hypertrophy and fibrosis in mice; at the same time, it increased myocardial FAD content, SCAD protein and mRNA expression levels, SCAD enzyme activity, myocardial ATP content, and decreased myocardial free fatty acid content (all P＜0.01). Conclusion Riboflavin can improve pathological myocardial hypertrophy and fibrosis in mice. This effect may be achieved by increasing myocardial FAD content, promoting myocardial SCAD expression, enhancing myocardial fatty acid β oxidation, and improving myocardial energy metabolism. |
| Key words: riboflavin short-chain acyl-CoA dehydrogenase energy metabolism pathological myocardial hypertrophy myocardial fibrosis |
