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改良线栓法大鼠大脑中动脉栓塞致缺血性脑卒中模型 6 小时内溶栓对急性脑梗死的影响。

Effects of thrombolysis within 6 hours on acute cerebral infarction in an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke.

机构信息

Department of Neurology, Shandong Provincial Qianfoshan Hospital, Affiliated to Shandong University, Jinan, Shandong, China.

Department of Emergency, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China.

出版信息

J Cell Mol Med. 2019 Apr;23(4):2468-2474. doi: 10.1111/jcmm.14120. Epub 2019 Jan 29.

Abstract

Recombinant tissue plasminogen activator (rt-PA) is the first-line drug for revascularization in acute cerebral infarction (ACI) treatment. In this study, an improved rat embolic middle cerebral artery occlusion model for ischaemic stroke was used and the rats were killed on the first, third and seventh day after model establishment. Increases in infarct volume were significantly less in the thrombolytic group than in the conventional group at every time-point. The microvascular density (MVD) in the thrombolytic group was significantly higher than that in the conventional group at every time-point, especially on the seventh day. Increases in the expressions of neuronal nitric-oxide synthase (NOS) and caspase-3 in the ischaemic region and in the nitric oxide contents, malondialdehyde contents, and inducible NOS activities in the cortex of infarct side were significantly less in the thrombolytic group than in the conventional group. Furthermore, decreases in the superoxide dismutase activities in the thrombolytic group were significantly less than those in the conventional group. In conclusion, thrombolytic rt-PA therapy within a broadened therapeutic window (6 hours) could significantly decrease the infarct volume after ACI, possibly by increasing MVD in the ischaemic region, decreasing apoptotic molecule expression, and alleviating the oxidative stress response.

摘要

重组组织型纤溶酶原激活剂(rt-PA)是急性脑梗死(ACI)治疗中再通的一线药物。本研究采用改良的大鼠大脑中动脉栓塞缺血性脑卒中模型,于模型建立后第 1、3、7 天处死大鼠。溶栓组各时间点梗死体积均明显小于常规组。溶栓组各时间点微血管密度(MVD)均明显高于常规组,尤其是第 7 天。缺血区神经元型一氧化氮合酶(NOS)和半胱氨酸天冬氨酸蛋白酶-3(caspase-3)表达以及梗死侧皮质中一氧化氮(NO)含量、丙二醛(MDA)含量和诱导型一氧化氮合酶(iNOS)活性的增加均明显小于常规组。溶栓组超氧化物歧化酶(SOD)活性降低也明显小于常规组。总之,在扩大的治疗窗(6 小时)内进行溶栓 rt-PA 治疗可显著降低 ACI 后的梗死体积,可能是通过增加缺血区的 MVD、减少凋亡分子的表达以及减轻氧化应激反应。

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