摘要
目的 以往有关脑缺血保护的研究大多集中于外源性干预措施,很少涉及缺血状态下脑的内源性保护作用。近年来研究发现,观察局灶脑缺血预处理对核因子- κB(nuclear factor- κB, NF -κB)及其靶基因基质金属蛋白酶- 9(matrix metalloproteinases, MMP -9)基因表达的影响。 方法 45只SD大鼠随机分为3组,其中预缺血组和假手术组分别在 2 h大脑中动脉阻塞(MCAO)及 22 h再灌注前3 d给予10 min的 IPC或假手术,对照组仅给予2次假手术,采用干湿重法、免疫组织化学和逆转录 多聚酶链反应(RT -PCR)技术比较各组脑含水量、NF- κB表达及 MMP- 9 的 mRNA转录。 结果 预缺血组NF κB免疫组化染色的积分吸光度值IA和MMP -9的mRNA表达水平均低于假手术组 (16 .098 2±1. 265. 3和23 565. 8±1978 .4,50 .7 %和84 .13%, P<0 .01),脑水肿亦轻于后者(缺血侧脑含水量:81. 7%和86 .4%, 非缺血侧脑含水量 77 .0%和 79. 3%, P均<0 .05)。 结论 局灶性 IPC可抑制NF -κB激活和MMP -9的基因转录,减轻脑水肿,NF- κB/ MMP -9下调可能是 IPC保护血脑屏障的分子机制之一。
Objective To investigate the effect of focal cerebral ischemic preconditioning (IPC) on brain edema and the expression of nuclear factor-κB( NF-κB) and its target gene MMP-9. Methods Forty-five SD rats were divided into 3 groups in which control group received sham surgery only, and the other two groups received 2 hours of middle cerebral artery occlusion (MCAO) followed by 22 hours of reperfusion with or without 10 minutes of IPC 3 days before. Brain water content, expression of NF-κB and MMP-9 mRNA were evaluated in each group by wet-dry weight method, immunohistochemistry staining and RT-PCR. Results Compared with the SS group, there was a lower NF-κB immunoreactivity and MMP-9 mRNA level (16 098.2±1 265.3 vs 23 565.8±1 978.4,50.7% vs 84.1%, P<0.01) as well as brain water content (ipsilateral:81.7% vs 86.4% and contralateral: 77.0% vs 79.3%, all P<0.05) in IPC group. Conclusions Ten minutes of IPC is strong enough to inhibit the activation of NF-κB and the transcription of MMP-9. Down-regulation of NF-κB/MMP-9 pathway might be a key event in the molecular mechanism of protection on blood-brain barrier (BBB) induced by focal IPC.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2005年第3期217-220,共4页
Chinese Journal of Geriatrics
