Peng Lin, William Fay
Department of Clinical Examination, Tianjin First Central Hospital, Tianjin 300192, China.
Zhonghua Xue Ye Xue Za Zhi. 2005 Nov;26(11):665-8.
To study the potential function and mechanism of heme oxygenase-1 (HO-1) in regulating platelet reactivity and arterial thrombosis.
HO-1-deficient (HO-1(-/-)) mice were generated by gene knock-out technique, and the genotyping of the mice was performed by PCR analysis of tail DNA. Thrombus formation was induced by applying FeCl(3) to the exposed carotid artery, and the occlusion time was monitored for each animal. Western blot and chemical assays were used to detect HO-1 and cGMP levels in platelets. Platelet aggregation induced by ADP was also studied.
The difference between mean occlusion time of wild-type mice [(15.56 +/- 1.25) min, n = 16] and HO-1(-/-) mice [(12.85 +/- 0.55) min, n = 14] was not statistically significant. However, after challenge with hemin, which induces HO-1 expression, mean occlusion time was significantly longer in wild-type mice [(16.25 +/- 1.20) min, n = 15] than in HO-1(-/-) mice [(11.96 +/- 0.98) min, n = 19; P < 0.05]. Hemin administration which induced oxidative stress could markedly elevate HO-1 level and cGMP concentration in platelet, while suppress ADP induced platelet aggregation in wild type mice.
Under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1 through the pathway of cGMP expression. It suggests that enhanced platelet HO-1 expression in response to physiological stress may represent an adaptive response mechanism to down-regulate platelet activation under pro-thrombotic conditions.
研究血红素加氧酶-1（HO-1）在调节血小板反应性和动脉血栓形成中的潜在作用及机制。
采用基因敲除技术构建HO-1基因缺陷（HO-1(-/-)）小鼠，通过对小鼠尾部DNA进行PCR分析进行基因分型。通过在暴露的颈动脉上应用FeCl(3)诱导血栓形成，监测每只动物的闭塞时间。采用蛋白质免疫印迹法和化学分析法检测血小板中HO-1和cGMP水平。还研究了ADP诱导的血小板聚集。
野生型小鼠的平均闭塞时间[（15.56±1.25）分钟，n = 16]与HO-1(-/-)小鼠[（12.85±0.55）分钟，n = 14]之间的差异无统计学意义。然而，在用诱导HO-1表达的血红素刺激后，野生型小鼠的平均闭塞时间[（16.25±1.20）分钟，n = 15]显著长于HO-1(-/-)小鼠[（11.96±0.98）分钟，n = 19；P < 0.05]。诱导氧化应激的血红素给药可显著提高血小板中HO-1水平和cGMP浓度，同时抑制野生型小鼠中ADP诱导的血小板聚集。
在刺激HO-1产生的条件下，HO-1通过cGMP表达途径抑制血小板依赖性血栓形成。这表明在血栓形成前状态下，生理应激反应增强的血小板HO-1表达可能代表一种下调血小板活化的适应性反应机制。
