Ritz Marie-Françoise, Ratajczak Philippe, Curin Yann, Cam Ertugrul, Mendelowitsch Aminadav, Pinet Florence, Andriantsitohaina Ramaroson
Neurosurgery Laboratory, Department of Research, University Hospital, Basel 4056, Switzerland.
J Nutr. 2008 Mar;138(3):519-25. doi: 10.1093/jn/138.3.519.
In this study, we investigated the in vivo effects of red wine polyphenol compounds (RWPC) in rats that were submitted to middle cerebral occlusion as an experimental model of stroke. Male Wistar rats were given RWPC [30 mg/(kg x d) dissolved in drinking water] or water for 1 wk before being subjected to transient middle cerebral artery occlusion followed by reperfusion. Sham-operated rats were subjected to transient occlusion in which the filament was not completely introduced. The release of amino acids and energy metabolites were monitored by intracerebral microdialysis. The volume of the ischemic lesion was assessed 24 h after reperfusion. Proteomic analysis of brain tissue was performed to study the effects of ischemia and RWPC on specific protein expression. Treatment with RWPC completely prevented the burst of excitatory amino acids that occurred in response to ischemia in untreated rats and significantly reduced brain infarct volumes. Rats chronically treated with RWPC, however, had lower basal concentrations of energy metabolites, including glucose and lactate in the brain parenchyma, compared with untreated rats. Chronic RWPC treatment significantly enhanced the residual cerebral blood flow during occlusion and reperfusion in rats subjected to transient occlusion compared with untreated rats. This effect resulted from arterial vasodilatation, as the internal diameters of several arteries were significantly enlarged after RWPC treatment. Proteomic studies revealed the modulation by RWPC of the expression of proteins involved in the maintenance of neuronal caliber and axon formation, in the protection against oxidative stress, and in energy metabolism. These findings provide an experimental basis for the beneficial effects of RWPC on the neurovascular unit during stroke.
在本研究中，我们以大脑中动脉闭塞的大鼠作为中风实验模型，研究了红酒多酚化合物（RWPC）的体内效应。雄性Wistar大鼠在接受短暂大脑中动脉闭塞再灌注之前，给予RWPC[30mg/(kg·d)溶解于饮用水中]或水，持续1周。假手术大鼠接受短暂闭塞，其中线栓未完全插入。通过脑内微透析监测氨基酸和能量代谢物的释放。再灌注24小时后评估缺血性损伤的体积。对脑组织进行蛋白质组学分析，以研究缺血和RWPC对特定蛋白质表达的影响。RWPC治疗完全阻止了未治疗大鼠缺血时出现的兴奋性氨基酸爆发，并显著减少了脑梗死体积。然而，与未治疗大鼠相比，长期接受RWPC治疗的大鼠脑实质中能量代谢物（包括葡萄糖和乳酸）的基础浓度较低。与未治疗大鼠相比，慢性RWPC治疗显著增强了短暂闭塞大鼠在闭塞和再灌注期间的残余脑血流量。这种效应是由动脉血管舒张引起的，因为RWPC治疗后几条动脉的内径显著增大。蛋白质组学研究揭示了RWPC对参与维持神经元管径和轴突形成、抗氧化应激保护以及能量代谢的蛋白质表达的调节作用。这些发现为RWPC在中风期间对神经血管单元的有益作用提供了实验依据。
