Liang Wang, Chuan-Zhen Lu, Qiang Dong, Jian Qiao, Hui-Min Ren, Bao-Guo Xiao
Institute of Neurology, Fudan University, 12 Wulumuqi Zhong Road, 200040, Shanghai, China.
Brain Res. 2004 Jul 23;1015(1-2):175-80. doi: 10.1016/j.brainres.2004.04.053.
The aim of this study is to investigate disturbances in fibrinolytic components in diabetic rats with middle cerebral artery occlusion (MCAO). Comparison of cerebral injury at 23 h after reperfusion indicated that infarction volumes were increased in diabetic rats as compared with normal rats. Cerebral ischemia/reperfusion in normal and diabetic rats was accompanied by increased expression of tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1) and neuroserpin (NSP) mRNA after reperfusion. Most importantly, the expression of NSP mRNA, but not t-PA, u-PA and PAI-1 mRNA, was reduced to undetectable levels at 11 and 23 h after reperfusion in diabetic rats as compared with normal rats. Although activity of PA (t-PA and u-PA) and the ratio of PA/PAI were increased at 5 h after reperfusion in both ischemic brains of diabetic and normal rats, the levels in diabetic rats were lower than that in normal rats. We speculate that the exacerbation of ischemic injury in diabetic rats may be related to the reduction of fibrinolytic component and the neuroprotective role of NSP. Further study of the efficacy of NSP in the pathogenesis and treatment of cerebral ischemia may provide novel insights.
本研究旨在探讨大脑中动脉闭塞（MCAO）糖尿病大鼠纤溶成分的紊乱情况。再灌注23小时后对脑损伤的比较表明，与正常大鼠相比，糖尿病大鼠的梗死体积增加。正常和糖尿病大鼠脑缺血/再灌注后，再灌注后组织型纤溶酶原激活剂（t-PA）、尿激酶型纤溶酶原激活剂（u-PA）、纤溶酶原激活剂抑制剂1（PAI-1）和神经丝氨酸蛋白酶（NSP）mRNA的表达均增加。最重要的是，与正常大鼠相比，糖尿病大鼠再灌注后11小时和23小时，NSP mRNA的表达降至不可检测水平，而t-PA、u-PA和PAI-1 mRNA的表达未下降。虽然糖尿病和正常大鼠缺血脑再灌注后5小时PA（t-PA和u-PA）活性及PA/PAI比值均升高，但糖尿病大鼠的水平低于正常大鼠。我们推测，糖尿病大鼠缺血损伤的加重可能与纤溶成分的减少及NSP的神经保护作用有关。进一步研究NSP在脑缺血发病机制和治疗中的疗效可能会提供新的见解。
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