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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。
Objective To investigate the effect of rosiglitazone (RSG) on cardiac hypertrophy induced by endothelin-1 (ET-1) and its mechanism. Methods The neonatal rat cardiomyocytes were treated with RSG (PPARγ agonist), GW9662 (PPARγ inhibitor) and Proteinki-naseC (PKC) pathway agonist (phorbol ester, PMA) and protein kinase C-channel blocker chelerythrine (chelerythrine, che) observed rosiglitazone in ET-1 and PMA-induced myocardial protein synthesis. Results After 2 days of culture, the DMEM protein content was (291 ± 13) mg / L in the control group (339 ± 15) mg / L and (329 ± 14) mg / L in the PMA group The levels of ET-1 + 10-7mol / LRSG group, ET-1 + 10-7mol / LRS group + GW9662 group and ET-1 + che group were 15% and 13% 291 ± 14) mg / L, (310 ± 13) mg / L and (291 ± 17) mg / L, respectively, and decreased by 13%, 8% and 13% , P <0.01). The protein content of PMA + 10-7mol / LRSG group decreased by 10% (P <0.01) compared with PMA group. PMA and ET-1 promote myocardial cell protein synthesis, RSG and che respectively inhibit protein synthesis, PPARγ blocker GW9662 weakened RSG inhibition. Determination of 3H-leucine incorporation in cardiomyocytes, RSG also inhibited cardiomyocyte hypertrophy induced by ET-1 and PMA, GW9662 can weaken the inhibitory effect of RSG. Conclusion RSG may have some relationship with the inhibition of ET-1-induced cardiac hypertrophy and PKC and peroxisome proliferator-activated receptor γ (PPARγ) pathway.