MMP-2、P53蛋白在大鼠实验性蛛网膜下腔出血后早期脑损伤中的作用研究

Study the Function of MMP-2 and P53 in the Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

目的:建立大鼠蛛网膜下腔出血(SAH)动物模型,检测脑组织中MMP-2及P53蛋白的表达水平及脑组织细胞凋亡情况,探讨MMP-2和P53蛋白在蛛网膜下腔出血后早期脑损伤中的作用机制。方法:72只SD大鼠随机分成假手术组、实验组。实验组又分为出血后12h、24h、48h、3d、5d共5个时相组,每个时相组各12只大鼠。各组标本分别检测MMP-2及P53蛋白在海马CA1区的表达水平,海马CA1区神经细胞凋亡情况。结果:实验组海马CA1区MMP-2、P53蛋白表达及凋亡细胞数较假手术组均有增高,以24、48h组更为显著。结论:MMP-2和P53蛋白在大鼠蛛网膜下腔出血后脑组织中表达明显增多,神经元细胞凋亡显著,两者与早期脑损伤关系密切,可能与MMP-2降解细胞外间质,破坏血脑屏障,导致血脑屏障通透性增高,P53蛋白诱导神经细胞凋亡有关。

Objective： To study the MMP-2 and P53 in the role of early brain injury after subarachnoid hemorrhage preliminary by detecting MMP-2 and P53 protein expression level and apoptosis in brain tissue in order to provide a theoretical basis for treatment of subarachnoid hemorrhage in clinical practice.Method： 72 clean-level male SD rats were randomly divided into sham-operated group （ n=12 ） and SAH group （ n=60 ） .SAH group were randomly divided into 12 h, 24 h, 48 h, 3 d and 5 d group, 12 rats in each group.The MMP-2 and P53 protein expression levels and neuroeyte apoptosis in hippocampus CA1 were detected.Result： The MMP-2, P53 protein and the number of apoptotic cells in hippocampus CA1 of SAH group in each time were increased compared with those of sham-operated group, the differences were the most significant at the 24 and 48 h group. Conclusion： MMP-2 and P53 protein are closely related to early brain injury after subarachnoid hemorrhage by the former, MMP-2 increasing the permeability of blood-brain barrier by degradation of extracellular matrix to destroy blood-brainbarrier, and the latter P53 protein, inducing the neurocyte apoptosis.