Uric acid enhances alteplase-mediated thrombolysis as an antioxidant.
Uric acid enhances alteplase-mediated thrombolysis as an antioxidant.
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DOI：
10.1038/s41598-018-34220-1
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发表时间：
2018-10-26
影响因子：
4.6
通讯作者：
Tancharoen S
中科院分区：
文献类型：
--
作者：
Kikuchi K;Setoyama K;Tanaka E;Otsuka S;Terashi T;Nakanishi K;Takada S;Sakakima H;Ampawong S;Kawahara KI;Nagasato T;Hosokawa K;Harada Y;Yamamoto M;Kamikokuryo C;Kiyama R;Morioka M;Ito T;Maruyama I;Tancharoen S
尿酸（UA）治疗可预防急性卒中溶栓患者的早期缺血性恶化。本研究的目的是通过使用新开发的基于微芯片的流动室测定法测量流动条件下的血栓溶解，检查UA对人血液样本中阿替普酶溶栓功效的影响。将健康志愿者的人血液样本暴露于UA、阿替普酶或UA和阿替普酶的组合。将全血和富血小板血浆灌注在胶原蛋白和促凝血酶原激酶包被的微芯片上，并用视频显微镜和流量压力传感器监测毛细血管阻塞。UA-阿替普酶治疗组30分钟时的曲线下面积（血栓形成或血栓溶解程度）比阿替普酶治疗组低92%。测量D-二聚体以评价人贫血小板血浆样品中的这些效应。虽然过氧化氢显著降低了阿替普酶对D-二聚体的升高，但UA显著抑制了过氧化氢的作用。同时，用阿替普酶或UA-阿替普酶联合治疗大鼠血栓栓塞性脑缺血模型。与单用阿替普酶相比，联合治疗可缩小梗死体积并抑制出血性转化。UA可能通过防止氧化应激而增强阿替普酶介导的血栓溶解，氧化应激抑制血栓中阿替普酶的纤维蛋白溶解。
Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 92% lower in the UA–alteplase-treated group compared with the alteplase-treated group. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA–alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.
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DOI：
10.1177/0271678x17709185
发表时间：
2017-11
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Percie du Sert N;Alfieri A;Allan SM;Carswell HV;Deuchar GA;Farr TD;Flecknell P;Gallagher L;Gibson CL;Haley MJ;Macleod MR;McColl BW;McCabe C;Morancho A;Moon LD;O'Neill MJ;Pérez de Puig I;Planas A;Ragan CI;Rosell A;Roy LA;Ryder KO;Simats A;Sena ES;Sutherland BA;Tricklebank MD;Trueman RC;Whitfield L;Wong R;Macrae IM
通讯作者：
Macrae IM
影响因子：
2.1
作者：
Lukic-Panin, Violeta;Deguchi, Kentaro;Abe, Koji
通讯作者：
Abe, Koji
影响因子：
3.7
作者：
Traby, Ludwig;Kollars, Marietta;Kyrle, Paul A.
通讯作者：
Kyrle, Paul A.
影响因子：
8.3
作者：
Amaro, Sergio;Soy, Dolors;Chamorro, Angel
通讯作者：
Chamorro, Angel
DOI：
10.1124/jpet.108.149484
发表时间：
2009-06-01
影响因子：
3.5
作者：
Kikuchi, Kiyoshi;Kawahara, Ko-ichi;Maruyama, Ikuro
通讯作者：
Maruyama, Ikuro