大鼠脑缺血再灌注后MMP-9的表达及人工合成E-选择素的干预作用

Expression of MMP-9 after Cerebral Ischemic Reperfusion and the Effects of Artificial Synthetic E-selectin in Rats

目的:研究肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶-9(MMP-9)参与大鼠脑缺血再灌注损伤的机制及人工合成E-选择素保护作用的机制。方法:健康SD大鼠,随机分为手术组、假手术组和治疗组。手术组建立大鼠局灶性脑缺血再灌注损伤模型;治疗组术前从股静脉注射人工合成E-选择素;假手术组仅将线栓插到颈外动脉、颈内动脉分叉处,其余步骤同手术组。免疫组化检测脑组织中TNF-α和MMP-9的表达,RT-PCR检测MMP-9 mRNA的表达。结果:手术组TNF-α、MMP-9和MMP-9 mRNA表达与假手术组比较均有明显升高(P<0.05);治疗组TNF-α、MMP-9和MMP-9 mRNA表达水平比手术组明显下降(P<0.05)。相关分析表明,MMP-9 mRNA分别与TNF-α和MMP-9的表达呈正相关。结论:大鼠脑缺血再灌注后TNF-α能够在转录水平诱导MMP-9的表达。人工合成E-选择素降低大鼠脑缺血再灌注后缺血脑组织MMP-9表达的机制可能是抑制TNF-α对MMP-9 mRNA合成的诱导,从而降低了MMP-9的表达。

Aim： To study the mechanisms of tumor necrosis factor-α and matrix metalloproteinases -9 in rat brain suffured with ischemia reperfusion injury and further explore the protective mechanism of artificial synthetic E-selectin in cerebral ischemia reperfusion injury model of rats. Methods： Healthy Sprague-Dawley rats were randomly divided into operation group, sham-operation group, artificial synthetic E-selectin treated group. The cerebral ischemia reperfusion injury model was established by inserting thread into middle cerebral artery. The treated group was established by the same method with operation group after the artificial synthetic E-selectin was injected into the femoral vein preoperation. The contents of TNF-α and MMP-9 expression in rat brain were measured by immunohistochemical methods, and MMP-9 mRNA was detected by reverse transcription PCR. Results： The expression of TNF-α, MMP-9 and MMP-9 mRNA in operation group were more than sham-operation group（P〈0.05）; the expression of TNF-α, MMP-9 and MMP-9 mRNA in treated group were less than operation group（P〈0.05）. Statistical results showed that the expression of MMP-9 mRNA was correlated with TNF-α and MMP-9 respectively. Conclusion： TNF-αinduces MMP-9 expression at transcriptional level in rats suffered with cerebral ischemia reperfusion injury. The protection mechanism of artificial synthetic E-selectin for cerebral ischemia reperfusion injury is probably that it inhibits the synthesis of MMP-9 mRNA which is induced by TNF-α at the transcriptional level, resulting in the decrease of MMP-9 expression.