阿司匹林通过脂多糖增加15-epi-lipoxin A4的产生，但阻断吡格列酮和阿托伐他汀对15-epi-lipoxin A4在大鼠心脏中的诱导作用。

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叶毅，林毅，黄明辉，黄明辉，黄明辉

阿司匹林通过脂多糖增加15-epi-lipoxin A4的产生，但阻断吡格列酮和阿托伐他汀对15-epi-lipoxin A4在大鼠心脏中的诱导作用。

前列腺素和其他脂质介质。2007年2月;83(1-2):89-98。Epub 2006年11月7日

PubMed ID

17259075 (PubMed视图

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摘要

阿司匹林(ASA)抑制环氧合酶-1，并通过Ser位点的乙酰化修饰环氧合酶-2 (COX2)(530)，导致PGH(2)的生成转变为15-R-HETE, PGH(2)是前列腺素的前体，15-R-HETE被5-脂氧合酶转化为15-epi-脂素a (4) (15-epi-LXA4)，这是一种有效的抗炎介质。阿托伐他汀(ATV)和吡格列酮(PIO)均可增加COX2的表达。ATV在Cys(526)上通过s -亚硝基化激活COX2，产生15-epi-LXA4和6-keto-PGF(1 α) (PGI的稳定代谢物)(2)。我们评估了ASA对脂多糖(LPS)或PIO+ATV诱导后心肌生成15-epi-LXA4和PGI(2)的影响。Sprague-Dawley大鼠预处理:对照;ASA 10 mg/kg;ASA 50 mg/kg;有限合伙人;LPS+ASA 10 mg/kg;LPS+ASA 50 mg/kg; 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.

引用这篇文章的药物银行数据

药物靶点

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