Heme-oxygenase induction inhibits arteriolar thrombosis in vivo: Effect of the, non-substrate inducer cobalt protoporphyrin

Heme-oxygenase induction inhibits arteriolar thrombosis in vivo: Effect of the, non-substrate inducer cobalt protoporphyrin
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DOI:
10.1016/j.ejphar.2008.12.030
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发表时间:
2009-03-15
影响因子:
5
通讯作者:
Jaye, Michael C.
Jaye, Michael C.
中科院分区:
医学2区
文献类型:
--
作者:
Johns, Douglas G.;Zelent, Dorothy;Jaye, Michael C.

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血红素加氧酶-1(1-10)代谢血红素形成血管扩张剂一氧化碳和抗氧化剂胆绿素。氯化血红素上调HO-1(也是一种底物)可减弱啮齿动物模型中的血栓形成,然而,保护作用是否是由于HO-1上调或底物可用性增加所致尚不清楚。本研究验证了以下假设:用钴原卟啉(COPP)(一种非底物HO-1诱导剂)治疗小鼠可保护内皮免受激光损伤。C57 B1/J6小鼠用载体、CoPP(20 mg/kg)、COPP加HO-1抑制剂锡原卟啉(SnPP; 20 mg/kg)或单独的SnPP处理18 h。活体显微镜用于定量响应于内皮的激光消融的提睾肌中的血栓形成。与载体相比,CoPP处理抑制血栓形成43%(P
Heme oxygenase-1 (1-10) metabolizes heme to form the vasodilator carbon monoxide and antioxidant biliverdin. Upregulation of HO-1 by hemin, which is also a substrate attenuates thrombosis in rodent models, however, whether protection is due to HO-1 upregulation of to increased substrate availability is unknown, This study tested the hypothesis that treatment of mice with cobalt protoporphyrin (COPP), a non-substrate HO-1 inducer, would protect the endothelium from laser injury. C57BI/J6 mice were treated with vehicle, CoPP (20 mg/kg), COPP plus the HO-1 inhibitor tin protoporphyrin (SnPP; 20 mg/kg) or SnPP alone for 18 h, Intravital microscopy Was used to quantitate thrombus formation in cremaster asterioles in response to laser ablation of the endothelium. CoPP treatment inhibited thrombosis by 43% compared to vehicle (P