过氧化体增殖物激活型受体β/δ激活剂抑制体外血管紧张素Ⅱ诱导的心肌细胞肥大  

Agonist of Peroxisome Proliferators Activated Receptor Beta/Delta Inhibits the Hypertrophy of Cardiac Myocytes by AngⅡ-Induced in Vitro

作　　者：盛莉[1] 叶平[1] 刘永学[2] 韩春光[2] 

机构地区：[1]中国人民解放军总医院老年心血管二科,北京市100853 [2]中国人民解放军军事医学科学院放射医学研究所药理毒理室,北京市100850

出　　处：《中国动脉硬化杂志》2007年第12期885-888,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30270551)

摘　　要：目的探讨过氧化体增殖物激活型受体β/δ激活剂GW0742在体外对血管紧张素Ⅱ诱导的肥大心肌细胞的作用,分析过氧化体增殖物激活型受体β/δ在其中的可能作用。方法体外培养新生大鼠的心室肌细胞,用血管紧张素Ⅱ诱导建立心肌肥厚模型,在模型中加入GW0742,用软件分析心肌细胞表面积观察心肌细胞面积,3H-亮氨酸的掺入检测心肌细胞蛋白合成速率及使用逆转录聚合酶链反应半定量测定心房钠尿肽、脑钠尿肽和过氧化体增殖物激活型受体β/δmRNA的表达变化,用免疫荧光方法测定过氧化体增殖物激活型受体β/δ的蛋白表达水平。结果血管紧张素Ⅱ可使体外培养的心肌细胞面积和3H-亮氨酸的掺入增加,升高心房钠尿肽和脑钠尿肽的表达,过氧化体增殖物激活型受体β/δ表达下降;GW0742可逆转上述变化。结论GW0742具有抑制血管紧张素Ⅱ诱导的体外心肌细胞肥大的作用,很可能通过活化过氧化体增殖物激活型受体β/δ途径。Aim To investigate the effects of agonist of peroxisome proliferators activated receptor beta/delta（PPAR β/δ） on angiotensin Ⅱ（AngⅡ）-induced hypertrophy myocytes and the changes of expressions of PPAR β/δ in vitro. Methods Hypertrophy in neonatal rat cardiac myocytes（MC） was established with AngⅡ and treated with GW0742.The surface area of MC was analyzed by the aid of NIH Image J software,and the synthetic rate of protein in MC was detected by 3 H-leucine incorporation.mRNA expression of atrial natriuretic peptide（ANP）,brain natriuretic peptide（BNP）,and PPAR β/δ was measured by reverse transcription-polymerase chain reaction（RT-PCR）.Protein expression of PPAR β/δ was detected by immunofluorescence staining.Results Changes induced by AngⅡ of MC were detected,including increases of surface area,mRNA expression of ANP,BNP,and 3 H-leucine incorporation;and decreases of mRNA and protein expressions of PPAR β/δ.Treatment with GW0742 inhibited the changes above.Conclusions The results demonstrate that GW0742,an agonist of PPAR β/δ,inhibits cardiac hypertrophy in vitro and suggest that GW0742 has a potential role in the prevention and treatment of cardiac diseases such as cardiac hypertrophy by activation of PPAR β/δ pathway.

关 键 词：内科学 过氧化体增殖物激活型受体 β/δ亚型 激活剂 心肌肥厚 心房钠尿肽 脑钠尿肽 

分 类 号：R5[医药卫生—内科学]