CAJ | 학술논문

目的观察非诺贝特是否可通过调控高迁移率族蛋白B-1(HMGB1)从而影响心肌肥厚的发生发展,并探讨其机制.方法体外培养乳鼠心肌细胞,采用逆转录-聚合酶链反应(RT-PCR)与Western blot法检测非诺贝特对心肌细胞内HMGB1表达水平及HMGB1核转位的影响;建立心肌肥大小鼠模型,分为非诺贝特组(n=5)与生理盐水组(n=5)进行比较,观察两组小鼠心肌细胞中HMGB1表达和转位,以及心肌肥大的进展.结果体外实验表明,过氧化物酶体增殖激活物受体-α(PPARα)激动剂非诺贝特具有下调乳鼠原代心肌细胞HMGB1的表达作用(RNA水平:P＜0.05;蛋白水平:P＜0.05),且该作用呈时间依赖性和剂量依赖性.研究还发现加入非诺贝特后心肌细胞释放HMGB1的能力降低(P＜0.05),并可以逆转炎症条件下的HMGB1高表达.体内实验进一步证明了非诺贝特可以下调肥大心肌细胞HMGB1的表达,并且促进其从胞质至胞核的转位过程.结论非诺贝特可能调控HMGB1在心肌细胞的表达与转位,从而调控心肌肥大疾病的进展.
목적 관찰비낙패특시부가통과조공고천이솔족단백B-1(HMGB1)종이영향심기비후적발생발전,병탐토기궤제.방법 체외배양유서심기세포,채용역전록-취합매련반응(RT-PCR)여Western blot법검측비낙패특대심기세포내HMGB1표체수평급HMGB1핵전위적영향;건립심기비대소서모형,분위비낙패특조(n=5)여생리염수조(n=5)진행비교,관찰량조소서심기세포중HMGB1표체화전위,이급심기비대적진전.결과 체외실험표명,과양화물매체증식격활물수체-α(PPARα)격동제비낙패특구유하조유서원대심기세포HMGB1적표체작용(RNA수평:P＜0.05;단백수평:P＜0.05),차해작용정시간의뢰성화제량의뢰성.연구환발현가입비낙패특후심기세포석방HMGB1적능력강저(P＜0.05),병가이역전염증조건하적HMGB1고표체.체내실험진일보증명료비낙패특가이하조비대심기세포HMGB1적표체,병차촉진기종포질지포핵적전위과정.결론 비낙패특가능조공HMGB1재심기세포적표체여전위,종이조공심기비대질병적진전.
Objective To investigate whether the regulation of high mobility group protein B-1 (HMGB1) by fenofibrate could affect the development of cardiac hypertrophy,and provide a preliminary study mechanism.Methods Primary cultured neonatal rat cardiomyocytes were used as the experimental subjects.The impacts of fenofibrarte on the level of HMGB1 expression and translocation in cardiomyocytes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Cardiac hypertrophy was induced in mice by thoracic transverse aortic constriction.The mice were divided into two groups:experimental group,fenofibrate administration (n =5),and control group,normal saline given (n =5).HMGB1 expression and translocation,as well as the progress of cardiac hypertrophy in the two groups were compared.Results Fenofibrate could down-regulate basal and LPS-stimulated HMGB1 expression (RNA level:P ＜0.05; Protein level:P ＜0.05),as well as the secretion of HMGB1 in cardiomyocytes (P ＜ 0.05).In addition,administration of fenofibrate to mice prevented the development of cardiac hypertrophy induced by thoracic transverse aortic constriction while increased levels of nuclear HMGB1.Conclusion Fenofibrate may inhibit the development of cardiac hypertrophy by regulating HMGB1 expression,which provides a new potential strategy to treat cardiac hypertrophy.