肉桂酸对早期心肌肥大的干预作用及促进脂肪酸转运的机制研究  

Effects and associated mechanisms of cinnamic acid on early cardiac hypertrophy and fatty acid transport

作　　者：崔艺萌 王玉珏 崔金刚[1,2] 陈瑜[1,2] 张腾[1,2] CUI Yimeng;WANG Yujue;CUI Jingang;CHEN Yu;ZHANG Teng(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Clinical Research Institute of Integrated Chinese and Western Medicine,Shanghai Academy of Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《中华中医药杂志》2024年第5期2181-2187,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82074049)。

摘　　要：目的:旨在明确桂枝的主要活性成分单体肉桂酸(CA)是否对主动脉缩窄(TAC)和苯肾上腺素(PE)诱导心肌肥大具有干预作用,并基于生物信息学分析进一步探讨CA发挥作用的相关分子机制。方法:体内实验:采用TAC手术构建小鼠心肌肥大模型,测算小鼠心脏质量指数,免疫荧光标记小麦胚芽凝集素(WGA)和心肌肥大标志物心房利钠肽(ANP)评估心肌肥大改变。HE、Masson’s Trichrome染色观察心脏病理损伤情况。体外实验:采用PE诱导原代心肌细胞(NRCMs)肥大模型评估CA是否具有直接的抗心肌肥大作用,罗丹明-鬼笔环肽和ANP染色评估心肌细胞肥大改变。RNA-seq分析差异基因。BODIPYTM 500/510染色评估脂肪酸转运能力。实时荧光定量PCR(qPCR)和蛋白质印迹(WB)法验证差异基因的表达。结果:体内实验:CA显著抑制TAC诱导的小鼠左心室重塑(P<0.05)。体外实验:CA显著抑制PE诱导的NRCMs肥大(P<0.05)。RNA-seq数据表明,脂肪酸转运途径及相关分子表达水平在PE组显著下调(P<0.05)。BODIPYTM 500/510染色结果提示CA显著抑制PE诱导的NRCMs脂肪酸转运能力降低(P<0.05)。qPCR和WB结果进一步验证CA显著抑制PE诱导NRCMs肉毒碱棕榈酰基转移酶1A(CPT1A)表达水平的降低(P<0.05)。结论:CA通过抑制早期心肌细胞肥大有效改善TAC诱导的左心室重塑,其机制可能部分基于上调CPT1A促进心肌细胞脂肪酸转运。Objective:To determine whether cinnamic acid(CA)plays a role in the pathological cardiac hypertrophy induced by transverse aortic constriction(TAC)and phenylephrine(PE),and based on the bioinformatics analysis,the corresponding mechanism were explored.Methods:TAC surgery was used to generate cardiac hypertrophy model in vivo.Cardiac hypertrophy was determined by heart mass index,wheat germ agglutinin(WGA)staining,and expression levels of cardiac hypertrophy markers,atrial natriuretic peptide(ANP).HE and Masson's Trichrome staining procedures were used to evaluate histopathologic changes.In vitro experiments were as follows:PE was adopted to induce cardiomyocyte hypertrophy in neonatal rat cardiomyocytes(NRCMs)in order to determine if CA was able to directly suppress cardiomyocyte hypertrophy.To detect hypertrophy induction,NRCMs were stained with rhodamine phalloidin and ANP.Differential gene expression was analyzed using RNA-seq data.Fatty acid transport was performed in NRCMs with BODIPYTM 500/510 probe.Real-time quantitative PCR(qPCR)and Western Blot(WB)were used to validate differential gene expression.Results:The in vivo findings:CA significantly antagonized TAC-induced left ventricular remodeling(P<0.05).In vitro findings:CA significantly suppressed PE-induced cardiomyocyte hypertrophy(P<0.05).RNA-seq analyses revealed that the expression of fatty acid transport-related genes was downregulated in PE-induced cardiomyocyte hypertrophy.And then BODIPYTM 500/510 staining demonstrated that CA significantly increased fatty acid transport in PE-induced cardiomyocyte hypertrophy(P<0.05).The results of qPCR and WB showed that CA significantly inhibited the decrease of CPT1A expression in PE-stimulated NRCMs(P<0.05).Conclusion:CA is effective at mitigating TAC-induced left ventricular remodeling in part by antagonizing the hypertrophic responses and promoting fatty acid transport through up-regulation of CPT1A in the PE-stimulated cardiomyocytes.

关 键 词：肉桂酸 心肌肥大 心力衰竭 左心室重塑 脂肪酸转运 肉毒碱棕榈酰基转移酶1A 

分 类 号：R285.5[医药卫生—中药学]