阿司匹林增加15-epi-lipoxin A4生产由脂多糖,但块吡格列酮和阿托伐他汀诱导鼠15-epi-lipoxin A4的心。

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林伯恩鲍姆Y, Y, Y, Freeberg SY,黄MH, Perez-Polo JR Uretsky男朋友

阿司匹林增加15-epi-lipoxin A4生产由脂多糖,但块吡格列酮和阿托伐他汀诱导鼠15-epi-lipoxin A4的心。

前列腺素其他脂质Mediat。2007年2月,83 (2):89 - 98。Epub 2006年11月7日。

PubMed ID

17259075 (在PubMed

]

文摘

阿司匹林(ASA)抑制cycloxygenase-1并修改cycloxygenase-2 (COX2)乙酰化在Ser(530),导致从生产PGH转移(2)、前列腺素的前体,15-R-HETE是转换通过5-lipoxygenase 15-epi-lipoxin (4) (15-epi-LXA4),一个强有力的抗炎介质。阿托伐他汀(ATV)和吡格列酮(PIO)增加COX2的表达。ATV激活S-nitrosylation COX2的半胱氨酸(526)生产15-epi-LXA4和6-keto-PGFα(1)(PGI的稳定代谢物(2))。我们评估了亚撒对心肌的影响生产15-epi-LXA4和PGI(2)在脂多糖诱导后(LPS)或PIO + ATV。Sprague-Dawley老鼠使用:控制;ASA 10毫克/公斤;ASA 50毫克/公斤;有限合伙人;有限合伙人+ ASA 10毫克/公斤;有限合伙人+ ASA 50毫克/公斤; LPS+ASA 200 mg/kg; PIO (10 mg/kg/d)+ATV (10 mg/kg/d); PIO+ATV+ASA 10 mg/kg; PIO+ATV+ASA 50 mg/kg; PIO+ATV+ASA 50 mg/kg+1400 W, a specific iNOS inhibitor; or PIO+ATV+1400 W. ASA alone had no effect on myocardial 15-epi-LXA4. LPS increased 15-epi-LXA4 and 6-keto-PGF(1alpha) levels. ASA (50 mg/kg and 200 mg/kg, but not 10 mg/kg) augmented the LPS effect on 15-epi-LXA4 but attenuated the effect on 6-keto-PGF(1alpha). PIO+ATV increased 15-epi-LXA4 and 6-keto-PGF(1alpha) levels. ASA and 1400 W attenuated the effects of PIO+ATV on 15-epi-LXA4 and 6-keto-PGF(1alpha). However, when both ASA and 1400 W were administered with PIO+ATV, there was a marked increase in 15-epi-LXA4, whereas the production of 6-keto-PGF(1alpha) was attenuated. In conclusion, COX2 acetylation by ASA shifts enzyme from producing 6-keto-PGF(1alpha) to 15-epi-LXA4. In contrast, S-nitrosylation by PIO+ASA augments the production of both 15-epi-LXA4 and 6-keto-PGF(1alpha). However, when COX2 is both acetylated and S-nitrosylated, it is inactivated. We suggest potential adverse interactions among statins, thiazolidinediones, and high-dose ASA.

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药物靶点

药物	目标	类	生物	药理作用	行动
乙酰水杨酸	前列腺素合成酶1 G / H	蛋白质	人类	是的	抑制剂	细节