Xanthotoxol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in a Rat Model of Focal Cerebral Ischemia
Xanthotoxol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in a Rat Model of Focal Cerebral Ischemia
复制标题
DOI：
10.1007/s10571-013-9939-2
复制
发表时间：
2013-07-01
影响因子：
4
通讯作者：
Liao, Fang
中科院分区：
文献类型：
--
作者：
He, Wei;Chen, Weiwei;Liao, Fang
我们之前发现蛇床中含有花椒毒酚，它是蛇床的主要活性成分之一。Cusson等通过减轻脑水肿、抑制中性粒细胞浸润、降低细胞间粘附分子-1（ICAM-1）和E-选择素的表达对大鼠局灶性脑缺血再灌注损伤具有保护作用。本研究旨在进一步确定花椒毒酚对脑缺血后神经保护作用的可能机制。采用大鼠大脑中动脉缺血2 h再灌注24 h的方法建立大鼠局灶性脑缺血再灌注模型。在缺血发作后1小时和12小时，腹腔内给予花椒毒酚（5和10 mg/kg）或溶媒。在再灌注后24小时，我们评估了花椒毒酚对血脑屏障（BBB）通透性、促炎介质如白细胞介素（IL）-1 β、肿瘤坏死因子（TNF）-α、IL-8、一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）、环氧合酶-2（考克斯-2）和转录因子p65亚基的产生的影响，核因子-κ B（NF-κ B）在缺血损伤后皮质中的表达。结果显示，与溶剂处理的动物相比，花椒毒酚处理显著减弱了BBB破坏，降低了IL-1 β、TNF-α、IL-8和NO水平，并减弱了iNOS活性。此外，花椒毒酚治疗还显著防止了缺血/再灌注诱导的iNOS、考克斯-2和核NF-κ B p65蛋白表达的增加。这些结果与我们以前的研究结果一起表明，花椒毒酚的神经保护作用可能归因于其减弱促炎介质表达的能力，从而抑制脑缺血后的炎症反应。
We previously found that xanthotoxol, one of the major active ingredients in Cnidium monnieri (L.) Cusson, exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema, inhibiting the neutrophil infiltration, and decreasing the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin. The present study was designed to further determine the possible mechanisms of action of neuroprotective properties of xanthotoxol after cerebral ischemia. Transient focal cerebral ischemia/reperfusion model in male Sprague-Dawley rats was induced by 2-h middle cerebral artery occlusion followed by 24-h reperfusion. Xanthotoxol (5 and 10 mg/kg) or vehicle were administered intraperitoneally at 1 and 12 h after the onset of ischemia. At 24 h after reperfusion, we assessed the effect of xanthotoxol on the blood-brain barrier (BBB) permeability, the production of pro-inflammatory mediators such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-8, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the p65 subunit of the transcription factor, nuclear factor-kappa B (NF-kappa B) in the cortex after ischemic insult. The results showed that xanthotoxol treatment significantly attenuated BBB disruption, reduced the IL-1 beta, TNF-alpha, IL-8 and NO level, and attenuated the iNOS activity compared with vehicle-treated animals. Further, xanthotoxol treatment also significantly prevented the ischemia/reperfusion-induced increase in the protein expression of iNOS, COX-2, and the nuclear NF-kappa B p65. These results, taken together with those of our previous study, suggest that the neuroprotection may be attributed to the ability of xanthotoxol to attenuate the expression of pro-inflammatory mediators and thereby inhibit the inflammatory response after cerebral ischemia.