Systemic use of argatroban reduces tumor mass, attenuates neurological deficits and prolongs survival time in rat glioma models.
Systemic use of argatroban reduces tumor mass, attenuates neurological deficits and prolongs survival time in rat glioma models.
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DOI：
10.1007/3-211-32318-x_82
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Y. Hua;L. Tang;M. Fewel;R. Keep;T. Schallert;K. Muraszko;J. Hoff;G. Xi
中科院分区：
文献类型：
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作者：
Y. Hua;L. Tang;M. Fewel;R. Keep;T. Schallert;K. Muraszko;J. Hoff;G. Xi
我们以前的研究表明，脑内灌注阿加曲班，一种特异性凝血酶抑制剂，减少脑水肿和神经功能缺损的C6胶质瘤模型。本研究调查了系统性阿加曲班给药是否可以减少C6和F98胶质瘤的胶质瘤质量和神经功能缺损，并延长生存时间。将大鼠C6或F98胶质瘤细胞注入成年雄性Fischer 344大鼠的右侧尾状核。在胶质瘤植入后立即将负载阿加曲班（0.3mg/h）或载体的渗透微型泵植入腹部。在第9天测定肿瘤质量。在实验期间，动物经历行为测试（前肢放置和前肢使用不对称）。此外，在F98胶质瘤模型中测试存活时间。在C6神经胶质瘤中，阿加曲班在第9天减少神经胶质瘤质量（p < 0.05）和神经功能缺损（p < 0.05）。在F98胶质瘤中，阿格拉曲班延长了存活时间（p < 0.05）并减少了体重减轻（84 ± 15克对载体组的99 ± 2克，P < 0.05）。总之，全身使用阿加曲班减少了肿瘤质量和神经功能缺损，延长了生存时间。这些结果表明，凝血酶在胶质瘤生长中起着关键作用，阿加曲班抑制凝血酶可能是胶质瘤的一种新治疗方法。
Our previous studies showed that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurological deficits in a C6 glioma model. The present study investigated whether systemic argatroban administration can reduce glioma mass and neurological deficits and extend survival time in C6 and F98 gliomas. Rat C6 or F98 glioma cells were infused into the right caudate of adult male Fischer 344 rats. Osmotic minipump loaded with argatroban (0.3 mg/hour) or vehicle was implanted into abdomen immediately after glioma implantation. Tumor mass was determined at day 9. Over the period of the experiment, the animals underwent behavioral testing (forelimb placing and forelimb use asymmetry). In addition, survival time was tested in the F98 glioma model. In C6 glioma, argatroban reduced glioma mass (p < 0.05) and neurological deficits (p < 0.05) at day 9. In F98 glioma, agratroban prolonged the survival time (p < 0.05) and reduced the body weight loss (84 ± 15 gram vs. 99 ± 2 gram in the vehicle group, P < 0.05). In conclusion, systemic use of argatroban reduced tumor mass and neurological deficits, and prolonged survival time. These results suggest that thrombin plays a key role in glioma growth and thrombin inhibition with argatroban may be a novel treatment for gliomas.