摘要
目的研究罗格列酮(rosiglitazone,RSG)抑制内皮素(endothelin-1,ET-1)诱发心肌肥大的作用及其机制。方法在培养新生大鼠心肌细胞中,采用RSG(PPARγ激动剂)、GW9662(PPARγ抑制剂)和蛋白激酶C(Proteinki-naseC、PKC)通路的激动剂(佛波醇酯,PMA)和蛋白激酶C通路的阻断剂白屈菜季氨碱(chelerythrine、che)观察罗格列酮在ET-1和PMA诱导心肌蛋白质合成中的影响。结果培养2d后,对照组(DMEM)蛋白质含量为(291±13)mg/L,ET-1组和PMA组分别为(339±15)mg/L和(329±14)mg/L,较对照组升高15%和13%(P<0.01);ET-1+10-7mol/LRSG组、ET-1+10-7mol/LRS组+GW9662组、ET-1+che组、分别为(292±14)mg/L,(310±13)mg/L,(291±17)mg/L;与ET-1组比较分别降低13%、8%、13%(P<0.01,P<0.05,P<0.01);PMA+10-7mol/LRSG组的蛋白含量较PMA组降低10%(P<0.01)。PMA和ET-1促进心肌细胞蛋白质的合成,RSG和che分别抑制蛋白质合成,PPARγ的阻断剂GW9662减弱RSG的抑制作用。测定心肌细胞的3H-亮氨酸掺入,RSG同样可以抑制ET-1和PMA诱导的心肌细胞肥大,GW9662可以削弱RSG的抑制作用。结论RSG抑制ET-1诱发的心肌肥大与PKC和过氧化物酶增值物激活受体γ(PPARγ)途径可能有一定关系。
AIM To investigate the inhibitory effects of Rosiglitazone （RSG） on ET-1-induced cardiac myocyte hypertrophy and the mechanism involved. METHODS We used the activator of PPAR3, （ RSG）, the inhibitor of PPARγ （ GW9662 ） and the inhibitor of protein kinase C （ PKC ） （ chelerythrine, che） to influence the protein synthesis stimulated by chronic ET-1 or PMA. RESULTS After two days＇ culture, the intracellular protein content in cardiac myocytes was （291 ± 13 ）mg/L in the control group, （339 ± 15） mg/L in the ET-1 group and （329 ± 14）mg/L in the PMA group （P 〈0.01 ）. ET-1 ＋ 10^-7 mol/L ＋ RSG group was （292 ± 14） mg/L, ET-1 ＋ 10^-7 mol/L ＋ RSG ＋ GW9662 group was （310 ± 13 ）mg/L and ET-1 ＋ che group was （291 ± 17 ）mg/L. Compared with that in the ET group, the intracellular protein content in cardiac myocytes decreased 13% , 8% and 13% respectively（ P 〈 0.01, P 〈0.05, P 〈0.01 ） and compared with that in the PMA group, the intracellular protein content in cardiac myocytes of PMA ＋ 10^-7 mol/L ＋ RSG group decreased 10% （ P 〈 0.01 ）. RSG inhibited the increasing effects of ET-1 and PMA-induced the promotion of protein content and 3 H-leucine incorporation on cardiac myocytes. GW9662 reduced the inhibitory effects of RSG on ET-1-induced hypertrophy in myocytes. CONCLUSION The inhibitory effects of RSG on ET-1 induced hypertrophy in myocytes are partially associated with PKC and PPARγ, pathway.
出处
《心脏杂志》
CAS
2007年第6期638-641,共4页
Chinese Heart Journal
