白藜芦醇预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用

Neuroprotective effects of preconditioning with resveratrol on focal cerebral ischemia-reperfusion injury in rats

目的探讨白藜芦醇(resveratrol,Res)预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用。方法♂SD大鼠45只,随机分为假手术组(Sham)、缺血/再灌注组(I/R)和白藜芦醇预处理缺血/再灌注组(Res+I/R),每组15只。采用线栓法行大脑中动脉阻断前脑血90min,拔出栓线实现再灌注。Res+I/R组缺血前30min腹腔注射白藜芦醇(30mg·kg-1)。再灌注后24h,用2,3,5-氯化三苯基四氮唑(TTC)染色显示梗死范围;再灌注72h后利用Morris水迷宫检测脑缺血后大鼠空间学习记忆能力,用电生理学方法检测白藜芦醇对脑缺血大鼠突触可塑性的影响。结果白藜芦醇预处理可以明显缩小脑梗死体积并改善大鼠的行为学障碍(P<0.05),在Morris水迷宫实验中Res+I/R组大鼠逃避潜伏期明显短于I/R灌注组(p<0.05),高频刺激后,I/R组海马CA1区NMDA受体依赖性的长时程增强(LTP)诱导障碍(n=5),Res+I/R组海马CA1区可诱导稳定的LTP(n=5)。结论缺血前30min白藜芦醇预处理对局灶性脑缺血/再灌注损伤具有神经保护作用,可以缩小脑梗死体积,并对大鼠的学习与记忆能力具有改善作用。

Aim To explore the neuroprotective effects of preconditioning with resveratrol on focal cerebral ischemia-reperfusion injury in rats.Methods Forty-five Sprague-Dawley rats were randomly divided into sham group,ischemic-reperfusion group（I/R）and resveratrol preconditioning ischemic-reperfusion group（Res＋I/R）.Each group had 15 animals.The middle cerebral artery in rats was occluded for 90 min by an intraluminal filament and then reperfused to cause transient focal cerebral ischemia.In the resveratrol preconditioning group,the resveratrol（30 mg·kg-1）was injected intraperitoneally 30 min before ischemia.Twenty-four hours after reperfusion,the infarct volume was shown with 2,3,5-triphenyl tetrazolium chloride（TTC）staining.The spatial learning and memory ability of rats was measured by Morris water maze 72 h after reperfusion.Electrophysiological recordings were conducted to detect the effects of resveratrol on Schaffer collateral-CA1 synaptic transmission in ischemic rats.Results The infarct volume and neurological score in Res＋I/R group were lower than I/R group（P0.05）.In the Morris water maze test,the escape latency period of rats in the Res＋I/R group was significantly shorter than that of the I/R group（P0.05）.Conditional protocol with high-frequency stimulation evoked a stable long-term potentiation（LTP）in hippocampus CA1 region in the Res＋I/R group rats（n=5）,however the LTP could not be induced with the same conditional protocol in the I/R group rats（n=5）.Conclusion The results suggest that the preconditioning with resveratrol 30 min before ischemia possesses neuroprotective effects on focal cerebral ischemia-reperfusion injury,which can reduce infarct volume and improve the ability of learning and memory in rats.