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目的:探索紫檀芪(pterostilbene,PTE)对小鼠脑缺血再灌注(IR)后线粒体氧化损伤的作用及可能机制。方法:通过双侧颈总动脉阻断法建立小鼠脑IR模型,腹腔注射PTE或Zn PP(血红素加氧酶-1抑制剂),动物随机均分为IR组、PTE+IR组、PTE+Zn PP+IR组、Zn PP+IR组,并且PTE有2.5 mg/kg、5 mg/kg、10 mg/kg三个剂量组。然后,进行神经功能评分;通过干湿比重法测定脑水肿;火焰光度法测定Na~+含量;Neu N和TUNEL法测定细胞存活和凋亡;通过线粒体膜电位(MMP)、线粒体活性氧(ROS)产物和线粒体复合物I和IV活性测定来检测线粒体的氧化应激损伤;通过Western Blot检测血红素加氧酶-1(HO-1)、NADPH醌氧化还原酶-1(NQO1)、谷胱甘肽S-转移酶(GST)、线粒体和胞浆细胞色素c蛋白的表达。结果:PTE可以提高小鼠的神经功能评分、减轻脑水肿和降低脑Na~+含量。PTE上调HO-1、NQO1和GST的表达,提高MMP、线粒体复合体I/IV活性和线粒体细胞色素c水平,减少线粒体ROS产物和降低胞浆细胞色素c水平,并且有一定的剂量依赖性。但是,PTE的这些作用可以被HO-1的抑制剂Zn PP逆转。结论:在脑IR模型小鼠,PTE通过激活HO-1信号减轻线粒体氧化应激损伤和细胞死亡,从而发挥脑保护作用。
Objective: To explore the effect and possible mechanism of pterostilbene (PTE) on mitochondrial oxidative damage after cerebral ischemia-reperfusion (IR) in mice. Methods: The brain IR model was established by bilateral common carotid artery occlusion. PTE or Zn PP (heme oxygenase-1 inhibitor) was intraperitoneally injected. The animals were randomly divided into IR group, PTE + IR group, PTE + Zn PP + IR group, Zn PP + IR group, and PTE 2.5 mg / kg, 5 mg / kg and 10 mg / kg. Then, the neurological function was evaluated; the cerebral edema was determined by the wet-dry proportion method; the Na ~ + content was determined by flame photometry; the survival and apoptosis of the cells were detected by Neu N and TUNEL; the mitochondrial reactive oxygen species ) And mitochondrial complex I and IV activity assay to detect mitochondrial oxidative stress injury; detected by Western Blot heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), glutathione Glycopeptide S-transferase (GST), expression of mitochondria and cytoplasmic cytochrome c protein. Results: PTE increased neurological score, reduced brain edema and decreased brain Na ~ + content. PTE upregulated the expression of HO-1, NQO1 and GST, increased MMP, mitochondrial complex I / IV activity and mitochondrial cytochrome c levels, decreased mitochondrial ROS production and decreased cytosolic cytochrome c levels in a dose-dependent manner. However, these effects of PTE can be reversed by Zn PP, an inhibitor of HO-1. CONCLUSIONS: PTE exerts neuroprotective effect in brain IR model mice by attenuating mitochondrial oxidative stress injury and cell death by activating HO-1 signaling.