MMP—2、P53蛋白在大鼠實驗性蛛網膜下腔出血后早期腦損傷中的作用研究

單宏寬　劉剛　徐法東

【摘要】 目的：建立大鼠蛛網膜下腔出血（SAH）動物模型，檢測腦組織中MMP-2及P53蛋白的表達水平及腦組織細胞凋亡情況，探討MMP-2和P53蛋白在蛛網膜下腔出血后早期腦損傷中的作用機制。方法：72只SD大鼠隨機分成假手術組、實驗組。實驗組又分為出血后12 h、24 h、48 h、3 d、5 d共5個時相組，每個時相組各12只大鼠。各組標本分別檢測MMP-2及P53蛋白在海馬CA1區的表達水平，海馬CA1區神經細胞凋亡情況。結果：實驗組海馬CA1區MMP-2、P53蛋白表達及凋亡細胞數較假手術組均有增高，以24、48 h組更為顯著。結論：MMP-2和P53蛋白在大鼠蛛網膜下腔出血后腦組織中表達明顯增多，神經元細胞凋亡顯著，兩者與早期腦損傷關系密切，可能與MMP-2降解細胞外間質，破壞血腦屏障，導致血腦屏障通透性增高，P53蛋白誘導神經細胞凋亡有關。

【關鍵詞】 蛛網膜下腔出血； MMP-2； P53蛋白； 細胞凋亡

【Abstract】 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 neurocyte 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-brain barrier，and the latter P53 protein，inducing the neurocyte apoptosis.

【Key words】 Subarachnoid hemorrhage； MMP-2； P53 protein； Apoptosis

First-authors address：Liaocheng Central Hospital of Shandong Province，Liaocheng 252000，China

doi：10.3969/j.issn.1674-4985.2017.25.008

蛛網膜下腔出血（subarachnoid hemorrhage，SAH）是神經系統常見的急危重癥，年發病率為（2～16）/10萬[1]，且近30年來發病率呈上升趨勢[2]，最常見的病因是顱內動脈瘤破裂，約占所有自發性蛛網膜下腔出血發病原因的34%[3-4]，約35%患者在SAH后24 h內死亡，與顱內動脈瘤破裂出血導致的早期腦損傷密切相關[5-6]，但SAH后早期腦損傷的機制卻知之甚少。SAH后多會出現腦水腫、顱內壓升高、腦血管痙攣及血-腦脊液屏障損壞等多種病理生理改變[7]。文獻[8]2004年提出，蛛網膜下腔出血后EBI是早期致死致殘的主要原因。相關研究認為EBI是多因素、多途徑的病理過程，其中神經細胞和血管內皮細胞凋亡起重要作用，但確切機制尚不明了[8-9]。……