重组人可溶性血栓调节蛋白对小鼠脑缺血/ 再灌注损伤的神经保护作用及机制研究

Neuroprotective effect of ART-123 on ischemia / reperfusion injury in mice and its mechanism

摘要:

目的 研究重组人可溶性血栓调节蛋白（ART-123）对小鼠脑缺血/ 再灌注损伤的影响。方法 BALB/c 小鼠行4 h 大脑中动脉闭塞（MCAO），再灌注时静脉注射Vehicle 或ART-123（1 或5 mg/kg）。再灌注24 h 后 评估小鼠脑梗死体积、运动协调、血浆高迁移率族蛋白（HMGB1）水平及出血量。结果 ART-123 可减少 MCAO 小鼠脑梗死体积，并呈剂量依赖性（F =4.843，P =0.038）。与Vehicle 组比较，ART-123（5 mg/kg）可 改善旋转试验中MCAO 小鼠运动协调（P =0.028）；降低血浆HMGB1 水平（P =0.000）。此外，Vehicle 组和 ART-123 组小鼠出血量差异无统计学意义（P >0.05）。结论 ART-123 可能通过抑制HMGB1 改善小鼠脑 缺血/ 再灌注损伤。

Abstract:

Objective To investigated the effects of recombinant human soluble thrombomodulin alpha (ART- 123) on cerebral ischemic/reperfusion injury in mouse model. Methods BALB/c mice were subjected to 4 h-middle cerebral artery suture occlusion (MCAO) and treated at reperfusion with Vehicle or ART-123 (1 or 5 mg/kg, i.v) after 4 h MCAO. Infarct volume, motor coordination, plasma high-mobility group box (HMGB1) level and hemorrhage volume were evaluated 24 h after 4 h MCAO. Results The infarct volume was reduced by ART-123 in mice subjected to 4 h MCAO in a dose-dependent manner (F = 4.843, P = 0.038). Moreover, ART-123 (5 mg/kg) improved motor coordination determined by the rotarod test (P = 0.028), and decreased plasma HMGB1 level compared with Vehicle-treated controls (P = 0.000). In addition, there was no difference in hemorrhage volume between Vehicletreated control group and the ART-123 treatment group. Conclusions ART-123 may improve cerebral ischemia / reperfusion injury in mice by inhibiting HMGB1.