Ding Yun-Hong, Mrizek Michael, Lai Qin, Wu Yimin, Reyes Raul, Li Jie, Davis William W, Ding Yuchuan
Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, Mail Code 7843, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Curr Neurovasc Res. 2006 Nov;3(4):263-71. doi: 10.2174/156720206778792911.
Exercise reduces ischemia and reperfusion injury in rat stroke models. We investigated whether gradual increases in tumor necrosis factor-alpha (TNF-alpha) reported during exercise down-regulates expression of TNF-alpha receptors I and II (TNFRI and II) in stroke, leading to reduced brain damage. Adult male Sprague Dawley rats were subjected to 30 minutes of exercise on a treadmill each day for 3 weeks. Then, stroke was induced by a 2-hour middle cerebral artery (MCA) occlusion using an intra-luminal filament. Expressions of TNFRI and II mRNA in the brain were detected using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Protein expressions of TNFRI and II were determined by enzyme-linked immunoabsorbant assay (ELISA) in serum and brain homogenates. Spatial distribution of TNF-alpha receptors in brain regions was determined with immunocytochemistry. In human umbilical vein endothelial cells (HUVEC), we addressed the causal effect of TNF-alpha pretreatment on TNF I and II expression using ELISA and real-time PCR. In exercised rats after stroke, brain infarct was significantly (p<0.01) reduced in the entire MCA supplied regions, associated with a mild expression of TNFRI and II mRNA and protein. The TNF-alpha receptors were restricted to the ischemic core. In contrast, a robust expression of TNFRI and II molecules was found in non-exercised rats subjected to similar ischemia/reperfusion insults. An in vitro study revealed a causal link between TNF-alpha pretreatment and reduced cellular expression of TNF-alpha receptors under hypoxic/reoxygenated conditions. Our results suggest that reduced-brain damage in ischemic rats after exercise preconditioning may be attributable to the reduced expression of TNF-alpha receptors. Chronically increased TNF-alpha expression was also found to reduce TNFI and II responding to acute ischemia/reperfusion insult.
运动可减轻大鼠中风模型中的缺血再灌注损伤。我们研究了运动期间报告的肿瘤坏死因子-α（TNF-α）逐渐增加是否会下调中风中TNF-α受体I和II（TNFRI和II）的表达，从而减少脑损伤。成年雄性Sprague Dawley大鼠每天在跑步机上运动30分钟，持续3周。然后，使用腔内细丝闭塞大脑中动脉（MCA）2小时诱导中风。使用实时逆转录聚合酶链反应（RT-PCR）检测脑中TNFRI和II mRNA的表达。通过酶联免疫吸附测定（ELISA）测定血清和脑匀浆中TNFRI和II的蛋白表达。用免疫细胞化学法测定脑区中TNF-α受体的空间分布。在人脐静脉内皮细胞（HUVEC）中，我们使用ELISA和实时PCR研究了TNF-α预处理对TNF I和II表达的因果效应。在中风后的运动大鼠中，整个MCA供血区域的脑梗死明显减少（p<0.01），同时TNFRI和II mRNA及蛋白表达轻度降低。TNF-α受体局限于缺血核心区。相比之下，在遭受类似缺血/再灌注损伤的未运动大鼠中发现TNFRI和II分子表达强烈。一项体外研究揭示了在缺氧/复氧条件下，TNF-α预处理与细胞TNF-α受体表达降低之间存在因果关系。我们的结果表明，运动预处理后缺血大鼠脑损伤减轻可能归因于TNF-α受体表达降低。还发现长期增加的TNF-α表达可降低TNFI和II对急性缺血/再灌注损伤的反应。
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