Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist.
Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist.
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使用腺病毒载体诱导白细胞介素 1 受体拮抗剂过度表达，减轻小鼠脑部缺血性炎症反应。
DOI：
10.1097/00004647-199808000-00004
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Betz,AL
中科院分区：
文献类型：
--
作者：
Yang,GY;Liu,XH;Kadoya,C;Zhao,YJ;Mao,Y;Davidson,BL;Betz,AL
已有研究表明，白介素1受体拮抗剂蛋白(IL-1ra)可减轻缺血性脑损伤，但白介素1(IL-1)在缺血性脑损伤中的作用机制尚不清楚。在本研究中，我们利用高表达人IL-1的小鼠来阐明IL-1在大脑中动脉闭塞(MCAO)后炎症反应的激活中的作用。髓过氧化物酶(MPO)活性和免疫组织化学染色作为多形核白细胞(PMNL)浸润的标志。将腺病毒载体(1×109粒)注入小鼠右侧脑室。五天后，使用缝线技术对小鼠进行大脑中动脉闭塞。在转RSVIL-1Ra、转RSVlacZ和生理盐水(对照组)的小鼠中，可持续24小时的大脑中动脉闭塞。用免疫组织化学方法检测髓过氧化物酶活性和MPO的定位。MCAO后2小时，Ad.RSVIL-1Ra、Ad.RSV-LacZ和生理盐水组小鼠脑表面血流量分别降至基础值的13.5%±3.4%、10.75%±2.6%和10.9%±2.6%。Ad.RSVlacZ组缺血侧MPO活性与生理盐水对照组相似(皮质：0.40±0.22比0.33±0.11；基底节：0.46±0.23比0.49±0.17；P>；0.05)，而Ad.RSVIL-1raA组MPO活性明显降低(皮质：0.18±0.07；基底节：0.26±0.15；P<；0.05)。髓过氧化物酶免疫组织化学结果显示，Ad.RSVIL-1Ra转基因小鼠脑缺血皮质、纹状体区和穹隆体区MPO阳性细胞的大量聚集明显减少。我们的结果表明，Ad.RSVIL-1Ra转基因小鼠为研究IL-1的作用机制提供了有用的工具。IL-1ra基因转基因小鼠局灶性脑缺血后24小时MPO活性测定和免疫染色均显著降低，提示IL-1可能在局灶性脑缺血时炎性细胞的活化中起重要作用。
It has been demonstrated that administration of an interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain injury; however, the detrimental mechanism initiated by interleukin-1 (IL-1) in ischemic brain injury is unclear. In this study, we used mice that were transfected to overexpress humanIL-1rato elucidate the role of IL-1 in the activation of the inflammatory response after middle cerebral artery occlusion (MCAO). Myeloperoxidase (MPO) activity and immunohistostaining were used as a marker of polymorphonuclear leukocytes (PMNL) infiltration. Adenoviral vector (1 × 109particles) was administered by injection into the right lateral ventricle in mice. Five days later, MCAO was performed on the mice using a suture technique. Permanent MCAO was achieved for 24 hours in the Ad.RSVIL-1ra-transfected, Ad.RSVlacZ-transfected, and saline (control) mice. Myeloperoxidase activity was quantified in each region and localization of MPO was determined by immunohistochemistry. After 2 hours of MCAO, the surface cerebral blood flow was reduced to 13.5% ± 3.4%, 10.75% ± 2.6%, and 10.9% ± 2.6% of baseline in the ischemic hemisphere in Ad.RSVIL-1ra-transfected, Ad.RSV-lacZ-transfected, and saline-treated mice, respectively. The MPO activity in the ischemic hemisphere in the Ad.RSVlacZgroup was similar to that in the saline control group (cortex: 0.40 ± 0.22 versus 0.33 ± 0.11; basal ganglia: 0.46 ± 0.23 versus 0.49 ± 0.17;P> 0.05); however, it was significantly reduced in the Ad.RSVIL-1ragroup (cortex: 0.18 ± 0.07; basal ganglia: 0.26 ± 0.15;P< 0.05). Myeloperoxidase immunohistochemistry showed that the massive accumulation of MPO-positive cells in the ischemic cortex, striatum, and corpus callosum regions was greatly attenuated in Ad.RSVIL-1ra-transfected mice. Our results indicate that Ad.RSVIL-1ra-transfected mice provide a useful tool to study the mechanism of action of IL-1. The MPO activity assay and immunostaining after 24 hours of focal ischemia were significantly reduced in IL-1ra gene-transfected mice, suggesting that IL-1 may play an important role in the activation of inflammatory cells during focal cerebral ischemia.