Anaya-Prado Roberto, Pérez-Gomez Nahum, Toledo-Pereyra Luis H, Walsh John, Jordan Jackie, Ward Peter A
Borgess Research Institute, Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI 49048, USA.
J Trauma. 2008 Sep;65(3):678-84. doi: 10.1097/TA.0b013e3181843f3a.
The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group): sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluated: brain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates.
中风的临床和实验治疗尚未取得与其他缺血/再灌注相关疾病相同的治疗成功。在本研究中，我们研究了小分子选择素抑制剂TBC-1269对全脑缺血（GCI）和控制性失血性休克（CHS）动物的影响。
48只体重在275克至300克之间的雄性Sprague-Dawley大鼠接受GCI和CHS模型实验。本研究包括三组动物（每组n = 16）：假手术/生理盐水组（第1组）；GCI/CHS/生理盐水组（第2组）；GCI/CHS/TBC-1269组（第3组）。实验设计包括双侧颈动脉闭塞20分钟，然后发展为CHS直至平均动脉压达到50 mmHg。20分钟时松开夹子，用生理盐水进行复苏，终点是使平均动脉压达到80 mmHg。复苏开始时的治疗包括生理盐水（第1组和第2组）或TBC-1269（25 mg/kg，第3组）。评估以下指标：脑组织髓过氧化物酶、缺血神经元平均数和7天生存率。
用TBC-1269治疗的动物脑组织髓过氧化物酶降低，尽管这种差异无统计学意义。治疗组动物的缺血神经元数量明显少于对照组。生存率也从对照组的40%提高到TBC-1269治疗组的80%。这种差异具有统计学意义。
小分子选择素抑制剂TBC-1269在该GCI和CHS模型中具有保护作用，缺血神经元数量减少和生存率提高证明了这一点。
