高脂血症对脑缺血再灌注大鼠脑组织中MMP-9和COX-2表达的影响

Effects of Hyperlipidemia on the Expressions of MMP-9 and COX-2 in Brain Tissues of Focal Cerebral Ischemia Reperfusion Rat Model

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。

Aim： To investigate the expressions of cyclooxygenase-2（COX-2） and matrix metalloproteinase-9 （MMP-9） after focal cerebral ischemia reperfusion（I/R） injury in hyperlipidemic（HL） rats and the effects of hyperlipidemia after focal cerebral ischemia reperfusion injury rat. Methods： 35 wistar rats were randomly divided into two groups： non-hyperlipidemia group and hyperlipidemia group. After the hyperlipidemic rats were made, they were randomly divided into three group： sham-operated group, non-hyperlipidemia ischemia reperfuion group（nI/R）, and hyperlipidemic ischemia reperfusion group（hI/R）. A middle cerebral artery occlusion model（MCAO） in rats was performed with Longa＇s method. The latter two were further divided into three subgroups according to reperfusion time interval of 12 h, 24 h, and 48 h after brain ischemia, 5 rats in each subgroup. Immunohistochemical staining were used to measure the expressions of MMP-9 and COX-2 in the brain tissue. HE staining were used to observe pathomorphological changes. Results： The expressions of MMP-9 and COX-2 in brain tissues of nI/R group and hI/R group were higher than in the sham-operated group（P0.01）. In the same IR time subgroup, the expressions of MMP-9 and COX-2 in hIR group were more than in nIR group（P0.01）. The expression of MMP-9 was positively correlated with the expression of COX-2. Conclusion： The expressions of MMP-9 and COX-2 are upgraded in ischemical reperfusion injury. Hyperlipidemia probably aggravate the ischemical reperfusion injury by increasing the expressions of MMP-9 and COX-2.