中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2014年
6期
1017-1022
,共6页
邹剑%周后凤%先志伟%刘培庆
鄒劍%週後鳳%先誌偉%劉培慶
추검%주후봉%선지위%류배경
血管紧张素Ⅱ%心肌细胞肥大%PPARα%NFATc4%p65-NFκB
血管緊張素Ⅱ%心肌細胞肥大%PPARα%NFATc4%p65-NFκB
혈관긴장소Ⅱ%심기세포비대%PPARα%NFATc4%p65-NFκB
Angiotensin Ⅱ%Cardiomyocyte hypertrophy%PPARα%NFATc4%p65-NFκB
目的：研究PPARα激动剂非诺贝特（ fenofibrate ）对血管紧张素Ⅱ（ AngⅡ）诱导的心肌细胞肥大的影响及机制。方法：在AngⅡ诱导的心肌细胞肥大模型中加入非诺贝特（10μmol／L）预处理1 h后，采用real-time PCR检测肥大标志物ANF、BNP和β-MHC mRNA水平变化，Western blotting检测NFATc4和p65-NFκB核转位的变化，免疫共沉淀检测心肌细胞核内p65-NFκB与NFATc4之间的相互作用， EMSA检测NFATc4在BNP启动子上DNA结合活性的变化。结果：非诺贝特可显著抑制AngⅡ诱导的心肌细胞肥大。非诺贝特可抑制AngⅡ诱导的NFATc4和p65-NFκB的入核，以及两者在核内的相互作用。非诺贝特可抑制AngⅡ诱导的NFATc4在BNP启动子上DNA结合活性的增加。结论：非诺贝特可增强心肌细胞核内PPARα与NFATc4之间的相互作用，并减弱p65-NFκB与NFATc4之间的相互结合，进而降低NFATc4在BNP启动子上的DNA结合活性，这可能是其抑制AngⅡ诱导的心肌肥大的重要机制。
目的：研究PPARα激動劑非諾貝特（ fenofibrate ）對血管緊張素Ⅱ（ AngⅡ）誘導的心肌細胞肥大的影響及機製。方法：在AngⅡ誘導的心肌細胞肥大模型中加入非諾貝特（10μmol／L）預處理1 h後，採用real-time PCR檢測肥大標誌物ANF、BNP和β-MHC mRNA水平變化，Western blotting檢測NFATc4和p65-NFκB覈轉位的變化，免疫共沉澱檢測心肌細胞覈內p65-NFκB與NFATc4之間的相互作用， EMSA檢測NFATc4在BNP啟動子上DNA結閤活性的變化。結果：非諾貝特可顯著抑製AngⅡ誘導的心肌細胞肥大。非諾貝特可抑製AngⅡ誘導的NFATc4和p65-NFκB的入覈，以及兩者在覈內的相互作用。非諾貝特可抑製AngⅡ誘導的NFATc4在BNP啟動子上DNA結閤活性的增加。結論：非諾貝特可增彊心肌細胞覈內PPARα與NFATc4之間的相互作用，併減弱p65-NFκB與NFATc4之間的相互結閤，進而降低NFATc4在BNP啟動子上的DNA結閤活性，這可能是其抑製AngⅡ誘導的心肌肥大的重要機製。
목적：연구PPARα격동제비낙패특（ fenofibrate ）대혈관긴장소Ⅱ（ AngⅡ）유도적심기세포비대적영향급궤제。방법：재AngⅡ유도적심기세포비대모형중가입비낙패특（10μmol／L）예처리1 h후，채용real-time PCR검측비대표지물ANF、BNP화β-MHC mRNA수평변화，Western blotting검측NFATc4화p65-NFκB핵전위적변화，면역공침정검측심기세포핵내p65-NFκB여NFATc4지간적상호작용， EMSA검측NFATc4재BNP계동자상DNA결합활성적변화。결과：비낙패특가현저억제AngⅡ유도적심기세포비대。비낙패특가억제AngⅡ유도적NFATc4화p65-NFκB적입핵，이급량자재핵내적상호작용。비낙패특가억제AngⅡ유도적NFATc4재BNP계동자상DNA결합활성적증가。결론：비낙패특가증강심기세포핵내PPARα여NFATc4지간적상호작용，병감약p65-NFκB여NFATc4지간적상호결합，진이강저NFATc4재BNP계동자상적DNA결합활성，저가능시기억제AngⅡ유도적심기비대적중요궤제。
AIM: To investigate the effects of fenofibrate on angiotensin Ⅱ ( AngⅡ)-induced cardiomyocyte hypertrophy .METHODS:Primary neonatal cardiomyocytes were pretreated with fenofibrate (10μmol/L) for 1 h followed by stimulation with AngⅡ(100 nmol/L).The mRNA levels of ANF, BNP andβ-MHC were measured by real-time PCR. Western blotting was employed to determine the nuclear translocations of NFATc 4 and p65-NFκB.Co-immunoprecipitation was used to investigate the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes .In addition, the DNA binding activity of NFATc4 on the BNP promoter was determined by EMSA .RESULTS:Fenofibrate significantly inhibited AngⅡ-induced cardiomyocyte hypertrophy .Fenofibrate treatment inhibited the nuclear translocations of NFATc 4 and p65-NFκB, as well as the interactions of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes induced by AngⅡ.Fenofi-brate inhibited the binding activity of NFATc 4 with the BNP promoter , which was strengthened by AngⅡ.CONCLU-SION:Fenofibrate enhances the interaction of NFATc 4 with PPARα, decreases the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes , and inhibits the DNA binding activity of NFATc 4 induced by AngⅡ, which may be the important mechanisms of fenofibrate on inhibiting cardiac hypertrophy .
