过氧化物酶体增殖物激活受体α激动剂对糜酶介导心肌纤维化的影响及机制初探  

Effect and Mechanism of Peroxisome Proliferator-Activated Receptor-α Agonist on Myocardial Fibrosis Induced by Chymase

作　　者：赵晓燕[1] 赵连友[2] 郑强荪[2] 张兴凯[1] 

机构地区：[1]解放军第五医院心内科,宁夏银川750004 [2]第四军医大学唐都医院心内科,陕西西安710038

出　　处：《中华高血压杂志》2010年第6期565-569,共5页Chinese Journal of Hypertension

摘　　要：背景过氧化物酶体增殖物激活受体α(PPARα)具有心血管保护作用,但其对心肌纤维化的影响及作用机制尚不清楚。目的初步探讨PPARα激动剂非诺贝特对糜酶介导的大鼠心脏成纤维细胞(CFs)增殖与胶原合成的影响及可能机制。方法用胰酶消化法分离、培养新生SD大鼠的CFs,采用3H胸腺嘧啶核苷(3H-TdR)掺入法测定DNA合成,3H脯氨酸掺入法测定胶原合成,RT-PCR和Western blot检测PPARα的mRNA及蛋白表达水平。结果非诺贝特以浓度依赖方式抑制糜酶介导的CFsDNA合成,其中50和100μmol/L非诺贝特预处理组的3H-TdR掺入量分别为(311±27)和(269±31)计数/(min.孔),均低于糜酶组[(393±46)计数/(min.孔),P<0.05和P<0.01]。随着非诺贝特浓度的增加,3H脯氨酸掺入量呈递减趋势,50和100μmol/L非诺贝特预处理组均显著低于糜酶组(均P<0.01)。非诺贝特以浓度依赖方式促进PPARα的mRNA和蛋白表达,50和100μmol/L非诺贝特预处理组均显著高于糜酶组(P<0.05和P<0.01)。结论非诺贝特通过抑制糜酶介导的大鼠CFs增殖和胶原合成发挥抗心肌纤维化作用,其机制可能与PPARα的基因和蛋白表达上调有关。Background Peroxisome proliferator-activated receptor-α （PPARα） has cardiovascular protective effect,but its effects on myocardial fibrosis and the underlying mechanism remain unclear. Objective To investigate the effect and possible mechanism of PPARα agonist fenofibrate on the proliferation and collagen synthesis of rat cardiac fibroblasts （CFs） induced by chymase. Methods Cultured CFs from neonatal SD rats were isolated by trypsinization. The DNA and collagen synthesis of CFs were evaluated by 3H-thymidine （3H-TdR） and 3H-proline incorporation,respectively. The mRNA and protein expressions of PPARα in CFs were determined by RT-PCR and Western blot. Results Pretreatment with fenofibrate inhibited the increase of CFs DNA synthesis induced by chymase in a dose-dependent manner. The 3H-TdR incorporation of CFs pretreated with 50 and 100 μmol/L fenofibrate were （311±27） and （269±31） count/（min·well）,which were significantly lower than that of the chymase group [（393±46）count/（min·well）,P〈0.05 and P〈0.01]. Pretreatment with fenofibrate decreased the 3H-proline incorporation in a concentration-dependent manner. The 3H-proline incorporation of CFs pretreated with 50 and 100 μmol/L fenofibrate were significantly lower than that of the chymase group（P〈0.01）. Pretreatment with 50 and 100 μmol/L fenofibrate obviously increased the mRNA and protein expressions of PPARα as compared with those of the chymase group（P〈0.05 and P〈0.01）. Conclusion Fenofibrate may inhibit the proliferation and collagen synthesis of rat CFs induced by chymase,resulting in inhibition of the process of myocardial fibrosis,which may be associated with the upregulation of PPARα mRNA and protein.

关 键 词：过氧化物酶体增殖物激活受体Α 非诺贝特 糜酶 心脏成纤维细胞 增殖 胶原 

分 类 号：R541[医药卫生—心血管疾病]