摘要
目的:探讨过氧化物酶增殖物激活受体α(PPARα)激动剂非诺贝特(fenofibrate)对糜酶介导的大鼠心脏成纤维细胞(CFs)增殖的影响及作用机制。方法:用胰酶消化法分离、培养新生SD大鼠的CFs。采用3H-脱氧胸腺嘧啶核苷(3H-TdR)掺入法测定CFs的DNA合成,用流式细胞术分析细胞周期,用RT-PCR检测PPARα及转化生长因子β1(TGF-β1)mRNA的表达。结果:①以不同浓度的非诺贝特预处理后,CFs的3H-TdR掺入量呈浓度依赖性减少,其中50和100μmol/L组均较糜酶组明显减少(分别为P<0.05和P<0.01)。②随着非诺贝特浓度的增加,CFs在G0/G1期的百分率逐渐增加,S期的百分率和增殖指数逐渐减少,其中50和100μmol/L组与糜酶组比较,上述各项指标均有显著性差异(分别为P<0.05和P<0.01)。③以25、50和100μmol/L非诺贝特预处理后,PPARαmRNA表达的水平呈浓度依赖性增加,其中50和100μmol/L组均较糜酶组显著增加(分别为P<0.05和P<0.01)。④随着非诺贝特浓度的增加,TGF-β1 mRNA表达水平呈递减趋势,其中50和100μmol/L组均较糜酶组明显减少(P<0.01)。结论:PPARα激动剂非诺贝特以浓度依赖的方式抑制糜酶诱导的大鼠CFs增殖的作用,其机制与PPARα基因表达的上调和TGF-β1基因表达的下调有关,提示PPARα和TGF-β1这两条信号通路可能存在信息交流。
AIM： To investigate the effect of peroxisome proliferator-activated receptor-α（PPARα） agonist fenofibrate on the proliferation of rat cardiac fibroblasts（CFs） induced by chymase and its mechanism of action.METHODS： Cultured CFs from neonatal SD rats were isolated by trypsinization and the DNA synthesis and cellular cycle of the CFs were evaluated,respectively,by 3H-TdR incorporation and flow cytometry.mRNA expressions of PPARα and TGF-β1 in the CFs were determined by RT-PCR.RESULTS： Pretreatment with fenofibrate decreased the 3H-TdR incorporation of the CFs in a concentration-dependent manner.The 3H-TdR incorporations pretreated with 50 and 100 μmol/L fenofibrate were significantly lower than those in the chymase group（P〈0.05,P〈0.01）.Cellular cycle analysis showed that pretreatment with 50 and 100 μmol/L fenofibrate markedly increased the cellular percentage in G0/G1 stage and decreased the cellular percentage in S stage and proliferation index compared with those in the chymase group（P〈0.05,P〈0.01）.Pretreatment with fenofibrate increased the PPARα mRNA and decreased the TGF-β1 mRNA in a dose-dependent manner.PPARα mRNA pretreated with 50 and 100 μmol/L fenofibrate was higher than in the chymase group（P〈0.05,P〈0.01） and the TGF-β1 mRNA was lower than in the chymase group（P〈0.01）.CONCLUSION： PPARα agonist fenofibrate inhibits the proliferation of rat CFs induced by chymase possibly through the upregulation of PPARα mRNA and the downregulation of TGF-β1 mRNA,suggesting that there may be cross-talk between the PPARα and TGF-β1 signal pathways.
出处
《心脏杂志》
CAS
2011年第1期11-15,共5页
Chinese Heart Journal
基金
陕西省科学技术研究发展计划项目资助(2005K13-G1-3)
