非诺贝特对新生大鼠体外肥大心肌细胞的影响

Effects of Fenofibrate on neonatal rat hypertrophic cardiomyocyte in vitro

目的:研究过氧化物酶体增殖物活化型受体α(PPARα)激活物非诺贝特对大鼠体外心肌细胞病理肥大的影响。方法:新生大鼠原代心肌细胞培养后,用不同时间、不同浓度的PPARα配体非诺贝特预处理细胞,然后以血管紧张素Ⅱ(AngⅡ)诱导其肥大。采用软件分析细胞面积,以RT-PCR法检测肥大心肌细胞α、β-肌球蛋白重链(α-MHC、β-MHC)及PPARαmRNA表达的影响,单四唑(MTT)比色法测定非诺贝特对AngⅡ处理细胞活力的干预作用。结果:非诺贝特预处理24 h可逆转AngⅡ诱导的心肌细胞肥大,α/β-MHC mRNA表达比值降低及细胞活力的改变,同时增加PPARαmRNA的表达,并呈一定剂量依赖性;而非诺贝特和AngⅡ几乎同时处理细胞时,则无明显效应。结论:PPARα参与心肌细胞肥大过程,长期慢性非诺贝特预处理可能对心肌有保护效应。

Objective ： To study the inhibitory effects of peroxisome proliferator-activated receptor α activator Fenofibrate on the angiotensin Ⅱ （Ang Ⅱ ）-induced cardiac hypertrophy in vitro. Methods： A model of hypertrophy of neonatal rat cardiac myocytes was established with Ang Ⅱ stimulation. With the aid of Leca Qwin Image software, the surface areas of cardiac myocytes were analyzed. The mRNA expression of α, β-myosin heavy chains（ α-MHC, β-MHC） and PPARα was measured by reverse transcription-polymerase chain reaction（ RT-PCR）, and the cultured myocyte viability was estimated by MTT assay. Results ： Fenofibrate pretreatment 24 h prior to Ang Ⅱ Significantly reduced Ang Ⅱ -induced cardiac hypertrophy, inhibited the effect of Ang Ⅱ on the cardiac myocyte viability and increased expression of α/β-MHC mRNA and PPARα mRNA in a dose-dependent manner. In contrast, Fenofibrate hadno significant effect on Ang Ⅱ treated cardiac myocytes when Fenofibrate treatment was concomitant with Ang Ⅱ. Conclusion： PPARα-dependent pathway was involved in the inhibition of cardiac hypertrophy, but chronic treatment was needed.