中国中西医结合杂志2024，Vol.44Issue(2)：175-182,8.DOI:10.7661/j.cjim.20230828.247
姜黄素下调高血压病大鼠心房颤动易感性及基于基因测序分子机制研究
Curcumin Alleviates Atrial Fibrillation Susceptibility in Hypertensive Rats and Intimate Molecular Mechanism Based on Gene Sequencing
摘要
Abstract
Objective To study the impacts of curcumin on susceptibility of hypertension associated-atrial fibrillation(AF),and to explore the underlying molecular mechanism.Methods Totally 45 12-week-old male SD rats were randomly divided into control group(n=15),abdominal aorta coarctation(AAC)model group(model group,n=15)and curcumin group(n=15).The AAC model was established in model group and curcumin group,while rats in the control group was not given AAC.Rats in the curcumin group were given 300 mg/(kg·d)curcumin by gavage for 4 weeks after AAC.Echocardiological,hemodynamic indexes,collagen volume fraction(CVF)and AF susceptibility were compared at 4 weeks after operation.The differently expressed mRNA extracted from left atrial tissues of the above 3 groups were quantified with high throughput sequencing.Then key molecular targets were identified by Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Ontology(GO)enrichment and protein-to-protein interact(PPI)analysis.Results In model group,the parameters including left atrial diameter(LAD),diastolic thickness of inter-ventricular septum(IVSd),systolic thickness of inter-ventricular septum(IVSs),maximum left ventricular pressure(LVP)max,LVPmin,maximum aortic pressure(AP)max,APmin,CVF of left atrial(LA-CVF),CVF of right atrial(RA-CVF),and ratiosor of individual AF,paroxysmal AF,non-self-terminating AF at high-right-atria(HRA)were higher than those in control group(P＜0.05,P＜0.01);while left ventricular ejection fraction(LVEF)and rate of left ventricular pressure change(LVdP/dt)max and |LVdP/dtmin | were lower than those in control group(P＜0.05,P＜0.01).Compared with model group,LAD,LVPmaxand LVPmin,APmax and APmin,LA-CVF and RA-CVF,ratios of individual AF,paroxysmal AF,non-self-terminating AF at HRA decreased,LVdP/dtmax and |LVdP/dtmin| increased in curcumin group(P＜0.05,P＜0.01).In summary,there were 7 305 differentially expressed genes among the 3 groups according to gene sequencing and bioinformation analysis of left atrial tissue.Based on KEGG,GO enrichment and PPI analysis,22 key molecular targets were selected finally which were associated with tricarboxylic acid cycle(TAC),mitochondrial respiratory chain and the fibroblast cycle regulation.Conclusions Curcumin administered by gavage for 4 weeks can effectively reduce LA and arterial pressure,atrial collagen deposition,LA diameter,and the susceptibility to AF in hypertensive rats.The underlying mechanism might involve in improvement of metabolic abnormality,mitochondrial function and in the fibroblast proliferation of left atrial tissue.关键词
心房颤动/高血压病/姜黄素/基因测序/成纤维细胞/中药单体Key words
atrial fibrillation/hypertension/curcumin/gene sequence/fibroblast/Chinese herbal monomer引用本文复制引用
姚青海,李曦铭,尤秉辰..姜黄素下调高血压病大鼠心房颤动易感性及基于基因测序分子机制研究[J].中国中西医结合杂志,2024,44(2):175-182,8.基金项目
天津市胸科医院院级课题(No.2018XKZ11) （No.2018XKZ11）
南开大学药物化学生物学重点实验室开放基金课题(No.2018080) （No.2018080）
天津市重点实验室建设项目(No.津科规[2022]5号) （No.津科规[2022]5号）
天津市医学重点建设学科项目(No.TJYXZDXK-018A,No.TJYXZDXK-049A,No.TJYXZDXK-055B) （No.TJYXZDXK-018A,No.TJYXZDXK-049A,No.TJYXZDXK-055B）
