摘要
目的 研究表明,脑缺血后基质金属蛋白酶（MMPs）可以破坏血脑屏障、促进脑水肿的形成及炎性细胞的浸润、加快神经细胞的死亡,从而加重缺血性脑损害。本研究观测MMPs抑制剂、KB-R7785对缺血性脑卒中的保护作用。方法 采用线段血管内栓塞大脑中动脉（MCAO）获得小鼠脑缺血模型。观察不同时间、剂量KB-R7785对24h后脑梗塞灶体积的影响,同时应用酶谱印迹技术检测缺血后脑组织中MMPs活性。结果 酶谱印迹显示MMP-9活性在缺血后6h表达增强,24h后达峰值。MCAO前30 min单次注射KB-R7785（100mg·kg-1）可显著抑制 MMP-9的活性;单次注射或缺血后1及4.5h分次注射KB-R7785（100mg·kg-1）均可明显减小脑梗塞体积（P<0.01）。结论MMP-9可促进脑梗塞形成;MMPs抑制剂、KB-R7785具有改善缺血性脑损伤作用。
Objective It had been suggested that matrix metalloproteinases (MMPs) were involved in brain damage after focal cerebral ischemia by disrupting the blood brain barrier, contributing to brain edema, facilitating invasion of inflammatory cell and promoting neuronal cell death. The present study was intended to investigate the effect of a new MMPs inhibitor, KB-R7785, on ischemic stroke. Methods Ischemia was induced by intraluminal permanent middle cerebral artery occlusion (MCAO). Animals were divided into groups according to the fashion of drug administration (dosage, time point, times of drug given). The infarction volumes were determined by coronal sections at 24 h after MCAO. The MMPs zymography was conducted with brain tissues from other separate mice subjected to ischemia. Results The zymogram showed that MMP-9 was activated initially 6 h after MCAO and maximized at 24 h after ischemia. Single injection of KB-R7785 (100 mg·kg-1) 30 min before MCAO significantly reduced both MMP-9 activity and infarct volume determined at 24 h. The KB-R7785 (100 mg·kg-1) given twice respectively at 1 and 4.5 h after MCAO also greatly decreased infarct volume. Conclusion The results suggest that the new MMPs inhibitor, KB-R7785 has a protective effect on ischemic brain injury, and provide further evidence that activated MMP-9 contributes to infarct formation after cerebral ischemia.
出处
《中华神经外科疾病研究杂志》
CAS
2002年第4期296-299,共4页
Chinese Journal of Neurosurgical Disease Research
基金
国家自然科学基金资助项目(3997026)
2000年度日中医学协会交流资助项目
