Department of Neurochemistry, Beijing Neurosurgical Institute, Beijing, China.
Transl Res. 2012 Sep;160(3):223-9. doi: 10.1016/j.trsl.2012.02.007. Epub 2012 Mar 3.
The dose-dependent protection of taurine against experimental stroke has been demonstrated previously. The objective of this study was to investigate the therapeutic window of taurine against experimental stroke, and the effects of delayed administration of taurine on inflammatory reaction in a rat model of stroke. Rats received 2-h ischemia by intraluminal filament, and then reperfused. Taurine (50 mg/kg) was administered intravenously 4 h, 8 h, 10 h, or 12 h after ischemia. The neurologic scores and the infarct volumes were evaluated 24 h after ischemia. Then, the effect of administration of taurine at 8 h after ischemia on the neutrophil infiltration in ischemic region was determined. Treatment with taurine 4 h or 8 h after ischemia significantly improved the neurologic function, and decreased the infarct volumes 24 h after ischemia. However, administration of taurine at 10 h or 12 h after ischemia had no significant neuroprotection. Further, taurine administered at 8 h after ischemia markedly reduced myeloperoxidase activity and attenuated neutrophil infiltration in ischemic region. Our data suggest that the therapeutic window of taurine against experimental stroke is of at least 8 h, and suppressing the neutrophil infiltration may be one of the mechanisms of delayed administration of taurine against experimental stroke.
先前已经证明牛磺酸对实验性中风具有剂量依赖性保护作用。本研究的目的是研究牛磺酸治疗实验性中风的治疗窗,以及牛磺酸延迟给药对中风大鼠模型炎症反应的影响。大鼠通过腔内纤维丝接受 2 小时的缺血,然后再灌注。缺血后 4 小时、8 小时、10 小时或 12 小时,静脉内给予牛磺酸(50mg/kg)。缺血后 24 小时评估神经功能评分和梗死体积。然后,确定缺血后 8 小时给予牛磺酸对缺血区域中性粒细胞浸润的影响。缺血后 4 小时或 8 小时给予牛磺酸治疗可显著改善神经功能,并降低缺血后 24 小时的梗死体积。然而,缺血后 10 小时或 12 小时给予牛磺酸则没有明显的神经保护作用。此外,缺血后 8 小时给予牛磺酸可显著降低髓过氧化物酶活性并减轻缺血区域中性粒细胞浸润。我们的数据表明,牛磺酸治疗实验性中风的治疗窗至少为 8 小时,抑制中性粒细胞浸润可能是牛磺酸延迟给药治疗实验性中风的机制之一。