Progress in Pathophysiological Mechanism of Matrix Metalloproteinases 9 and its Gene Polymorphism in Ischemic Cerebral Injury

doi:10.3969/j.issn.1673-5765.2019.05.020

Abstract

Abstract:

When ischemic stroke occurs, matrix metalloproteinases 9 (MMP9) has been shown to be highly expressed in infarct lesion and surrounding cerebral tissue, and neutrophils will be highly expressed in perivascular around infarct focus and peripheral blood. Polymerase δ-interacting protein 2, interleukin17 (IL-17), tumor necrosis factor alpha, IL-1β, cardiovascular active peptide, vascular endothelial growth factor may promote the expression of MMP9 through p38 mitogen activated protein kinases (MAPK), extracellular regulated protein kinases 1/2-dependent nuclear factor κB (NF-κB) and activated protein 1, p42/p44MAPK, c-Jun N-terminal kinase, p65-NF-κB and other pathways. The high expression of MMP 9 is closely related to hemorrhagic transformation in ischemic stroke. The MMP9 level in peripheral blood is closely correlated with ischemic stroke severity, and is an independent risk factor for death and symptomatic intracranial hemorrhage in patients with rt-PA thrombolysis, and related to poor outcome of ischemic stroke patients. The gene locus polymorphism of MMP9 rs3918242 may be associated with the risk of ischemic stroke and the disease severity, but current research results are still inconsistent.

Key words: Stroke; Matrix metallopeptidase 9; Polymorphism; Hemorrhagic transformation

摘要：

基质金属蛋白酶9（matrix metalloproteinases 9，MMP9）被证明在缺血性卒中患者梗死灶及梗死灶周围脑组织，梗死灶血管周围及外周血中性粒细胞中均高表达。聚合酶δ-相互作用蛋白2、白细胞介素17（interleukin17，IL-17）、肿瘤坏死因子α、IL-1β、心血管活性肽、血管内皮生长因子等可通过p38丝裂原活化蛋白激酶（mitogen activated protein kinases，MAPK）、细胞外调节蛋白激酶1/2依赖的核因子κB（nuclear factor κB，NF-κB）和活化蛋白-1、p42/p44MAPK、c-Jun氨基末端激酶、p65- NF-κB等不同途径促进MMP9的表达。MMP9的高表达与缺血性卒中出血转化关系密切，且外周血 MMP9水平变化与rt-PA溶栓患者死亡或症状性颅内出血独立相关，与缺血性卒中严重程度及不良功能结局相关。MMP9 rs3918242位点基因多态性与缺血性卒中的风险及疾病严重程度可能相关，但目前研究的结果和结论尚不一致。

关键词: 卒中; 基质金属蛋白酶9; 基因多态性; 出血转化

ZHANG Min, MA Li, ZHAO Yong-Mei, LYU Yan-Min, LONG Hui-Deng, PANG Li-Juan. Progress in Pathophysiological Mechanism of Matrix Metalloproteinases 9 and its Gene Polymorphism in Ischemic Cerebral Injury[J]. Chinese Journal of Stroke, 2019, 14(05): 504-510.

张敏，马丽，赵咏梅，吕燕敏，龙会登，庞丽娟. 基质金属蛋白酶及其基因多态性在缺血性卒中病理过程中的作用[J]. 中国卒中杂志, 2019, 14(05): 504-510.

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