Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice.
Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice.
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非布索坦抑制黄嘌呤氧化酶可减轻小鼠收缩期超负荷引起的左心室肥大和功能障碍。
DOI：
10.1016/j.cardfail.2008.06.006
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发表时间：
2008-11
影响因子：
6
通讯作者：
Chen, Yingjie
中科院分区：
文献类型：
--
作者：
Xu, Xin;Hu, Xinli;Lu, Zhongbing;Zhang, Ping;Zhao, Lin;Wessale, Jerry L.;Bache, Robert J.;Chen, Yingjie
嘌呤类似物黄嘌呤氧化酶（XO）抑制剂（XOI）别嘌呤醇和氧嘌呤醇已被报道可预防继发于心肌梗死或快速心室起搏的心力衰竭。由于这些药物可能影响嘌呤代谢的其他方面，从而影响其作用，因此本研究检查了非嘌呤XOI非布司他对压力超负荷诱导的左心室（LV）肥大和功能障碍的影响。小鼠的横向主动脉缩窄（TAC）在第8天引起LV肥大和功能障碍以及心肌硝基酪氨酸增加。TAC还引起磷酸化Akt（p-AktSer 473）、p42/44细胞外信号调节激酶（p-ErkThr 202/Tyr 204）和哺乳动物雷帕霉素靶蛋白（mTOR）（p-mTORSer 2488）的增加。在TAC后约60分钟开始使用非布司他（5 mg/kg/天，灌胃8天）抑制XO可减轻TAC诱导的LV肥大和功能障碍。非布司他减弱了TAC诱导的硝基酪氨酸（表明心肌氧化应激降低）、p-ErkThr 202/Tyr 204和p-mTORSer 2488的增加，对总Erk或总mTOR无影响。非布司他对心肌p-AktSer 473或总Akt无影响。结果表明，XO抑制与非布司他降低了氧化应激的压力超载LV，从而减少了激活的途径，导致病理性肥大和收缩功能障碍。
The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mice caused LV hypertrophy and dysfunction as well as increased myocardial nitrotyrosine at 8 days. TAC also caused increased phosphorylated Akt (p-AktSer473), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204) and mammalian target of rapamycin (mTOR) (p-mTORSer2488). XO inhibition with febuxostat (5mg/kg/day by gavage for 8 days) beginning ~60 minutes after TAC attenuated the TAC-induced LV hypertrophy and dysfunction. Febuxostat blunted the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-ErkThr202/Tyr204 and p-mTORSer2488, with no effect on total Erk or total mTOR. Febuxostat had no effect on myocardial p-AktSer473 or total Akt. The results suggest that XO inhibition with febuxostat reduced oxidative stress in the pressure overloaded LV, thereby diminishing the activation of pathways that result in pathologic hypertrophy and contractile dysfunction.
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影响因子：
3
作者：
Hou, Mingxiao;Hu, Qingsong;Bache, Robert J.
通讯作者：
Bache, Robert J.
影响因子：
20.1
作者：
Ide, T;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A
DOI：
10.1152/ajpheart.00831.2005
发表时间：
2006-02-01
影响因子：
4.8
作者：
Naumova, AV;Chacko, VP;Weiss, RG
通讯作者：
Weiss, RG
影响因子：
7.4
作者：
BINDOLI, A;CAVALLINI, L;DILISA, F
通讯作者：
DILISA, F
影响因子：
6
作者：
Hayashi, Keiko;Kimata, Hirotaka;Nagata, Kohzo
通讯作者：
Nagata, Kohzo