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目的:观察高脂血症对脑缺血/再灌注(I/R)大鼠脑组织中基质金属蛋白酶-9(MMP-9)、环氧化物酶-2(COX-2)表达的影响,探讨高脂血症在I/R损伤中的作用。方法:雄性健康Wister大鼠35只,随机分为非高脂血症组和高脂血症组(制备高脂血症模型)。成模后再随机分为3组:假手术组;正常血脂缺血再灌注组(nI/R组);高脂缺血再灌注组(hI/R组)。应用线栓法制做大鼠大脑中动脉栓塞模型,nI/R组和hI/R组又分为缺血1h再灌注12、24和48h3个时间点组,每时间点均n=5只。用免疫组化法检测脑组织中MMP-9、COX-2的表达和脑组织苏木精-伊红染色以观察病理形态的改变。结果:hI/R组和nI/R组中MMP-9、COX-2的表达均比假手术组高(P<0.01)。同一缺血再灌注时间点,hI/R组脑组织中MMP-9、COX-2的表达高于nI/R组(P<0.01)。缺血脑组织中MMP-9与COX-2的表达呈显著正相关。结论:MMP-9、COX-2在大鼠脑I/R后表达增加,提示参与I/R损伤后的炎症反应。高脂血症可能作为一种致炎状态使脑MMP-9、COX-2表达增加,并且通过增加脑I/R后MMP-9、COX-2的表达加重I/R损伤。
Objective: To observe the effect of hyperlipidemia on the expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) in cerebral ischemia / reperfusion (I / R) To investigate the role of hyperlipidemia in I / R injury. Methods: Thirty - five male Wister rats were randomly divided into non - hyperlipidemia group and hyperlipidemia group (hyperlipidemia model). The rats in the model group were randomly divided into three groups: sham operation group, normol-ischemia reperfusion group (nI / R group) and hypercholesterolemic ischemia reperfusion group (hI / R group). The model of middle cerebral artery occlusion (MCAO) was established by thread occlusion. The rats in nI / R group and hI / R group were further divided into 3 groups at 12h, 24h and 48h after reperfusion for 1h, n = 5 each time point. Immunohistochemistry was used to detect the expression of MMP-9 and COX-2 in brain tissue and brain tissue hematoxylin-eosin staining to observe the pathological changes. Results: The expressions of MMP-9 and COX-2 in hI / R group and nI / R group were significantly higher than those in sham operation group (P <0.01). At the same time of ischemia-reperfusion, the expression of MMP-9 and COX-2 in hI / R group was higher than that in nI / R group (P <0.01). There was a significant positive correlation between MMP-9 and COX-2 expression in ischemic brain tissue. Conclusion: The expression of MMP-9 and COX-2 in rat brain after I / R is increased, suggesting that they are involved in the inflammatory reaction after I / R injury. Hyperlipidemia may increase brain MMP-9, COX-2 expression as a proinflammatory state, and aggravate I / R injury by increasing the expression of MMP-9 and COX-2 after cerebral I / R.