过氧化物酶体增殖物激活型受体激活剂对新生大鼠心肌细胞肿瘤坏死因子-α的影响  

Effects of peroxisome proliferator-activated receptor activators on tumor necrosis factor-α expression in neonatal rat cardiac myocytes

作　　者：方红[1] 周新[1] 叶平[2] 贺艳丽[1] 王琼[3] 高月[3] 刘永学[3] 

机构地区：[1]武汉大学中南医院基因诊断中心,武汉430071 [2]解放军总医院老年心内科,北京100853 [3]北京放射医学研究所药理毒理室,北京100850

出　　处：《军事医学科学院院刊》2003年第2期89-91,95,共4页Bulletin of the Academy of Military Medical Sciences

基　　金：全军"十五"计划面上课题资助项目 (0 2M0 12 )

摘　　要：目的 :探讨过氧化物酶体增殖物激活型受体 (peroxisomeproliferator_activatedreceptors ,PPARs)激活剂对新生大鼠心肌细胞肿瘤坏死因子_α(tumornecrosisfactor_α ,TNFα)和PPARs自身表达水平的影响。方法 :体外原代培养新生Wistar大鼠心肌细胞 ,分别给予不同浓度的非诺贝特 (PPARα激活剂 )或吡格列酮 (PPARγ激活剂 )刺激 ,并辅加脂多糖诱导TNFα表达。采用半定量RT_PCR法检测TNFα ,PPARα及PPARγmRNA的表达 ,ELISA法检测TNFα的蛋白水平 ,Western印迹法检测PPARα和PPARγ蛋白表达。结果 :与对照组相比 ,非诺贝特组和吡格列酮组的TNFαmRNA及蛋白表达水平均明显降低 ,且呈剂量依赖性。而相应PPARα和PPARγ表达则无显著变化。结论 :PPARα和PPARγ激活剂可显著抑制新生大鼠心肌细胞中脂多糖诱导的TNFα表达 ,PPARα和PPARγ活化后发挥抗炎作用 。Objective:To explore the effects of peroxisome proliferator_activated receptor (PPAR) activators on tumor necrosis factor_α(TNFα) and PPARs expressions in neonatal rat cardiac myocytes.Methods:Primary cultures of cardiac myocytes were prepared from ventricles of 3_day_old Wistar rats. Cardiac myocytes were pretreated with PPARα activator(fenofibrate)or PPARγ activator (pioglitazone)at different concentrations and then stimulated with lipopolysaccharide (LPS,10?ng/ml). Reverse transcription_polymerase chain reaction(RT_PCR)was used to examine TNFα, PPARα and PPARγ mRNA levels. TNFα was determined by ELISA,while PPARα and PPARγ were measured by Western blotting.Results:The results of RT_PCR demonstrated that pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS_induced TNFα mRNA expression in concentration dependent manner and also decreased LPS_induced TNFα protein expression in medium. However, no significant changes were observed on PPARα or PPARγ mRNA and protein expression. Conclusions:These results suggest that PPARα and PPARγ activators inhibit cardiac TNFα expression but not accompanied by the changes in PPARα or PPARγ themselves. PPARα and PPARγ activators appear to play a role in the control of the inflammatory response not by changing the receptor expression themselves.

关 键 词：心肌细胞 肿瘤坏死因子-Α 过氧化物酶体增殖物激活型受体激活剂 抗炎药物 

分 类 号：R541[医药卫生—心血管疾病]