Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury.
Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury.
复制标题
虎杖甙对大鼠大脑皮层缺血/再灌注损伤后线粒体依赖性细胞凋亡的神经保护作用。
DOI：
10.3892/mmr.2016.5936
复制
发表时间：
2016-12
影响因子：
3.4
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Gao Y;Chen T;Lei X;Li Y;Dai X;Cao Y;Ding Q;Lei X;Li T;Lin X
白藜芦醇苷（PD）对失血性休克诱导的线粒体损伤的神经保护作用已被描述，据报道，缺血性卒中涉及线粒体功能障碍和细胞凋亡。在本研究中，PD在防止细胞凋亡的神经保护作用进行了评估后，诱导局灶性脑缺血大鼠大脑中动脉闭塞（MCAO）。在缺血/再灌注（I/R）损伤前10分钟通过尾静脉注射给予PD（30 mg/kg）。缺血再灌注损伤后24 h，PD治疗组改良神经功能评分（mNSS）改善，梗死体积缩小。末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色和Annexin V/碘化丙啶测定证实了PD在缺血皮质中的抗凋亡作用。此外，PD改善I/R损伤诱导的线粒体功能障碍，反映了形态学观察和线粒体膜电位和细胞内ATP测量的测量。Western印迹分析显示，与溶剂处理组相比，PD组中B细胞淋巴瘤2凋亡调节因子（Bcl-2）表达增加，Bcl-2相关蛋白X凋亡调节因子表达减少。PD处理还阻止了细胞色素c从线粒体释放到细胞质中，并减弱了caspase-9和caspase-3的活性。此外，PD治疗降低了从缺血皮层分离的神经元中活性氧的水平。因此，本研究的结果表明，PD具有双重作用，改善氧化应激和细胞凋亡，使其成为治疗缺血性卒中的一种有前途的新疗法。
The neuroprotective effect of polydatin (PD) against hemorrhagic shock-induced mitochondrial injury has been described previously, and mitochondrial dysfunction and apoptosis were reportedly involved in ischemic stroke. In the present study the neuroprotective effect of PD in preventing apoptosis was evaluated following induction of focal cerebral ischemia by middle cerebral artery occlusion (MCAO) in rats. PD (30 mg/kg) was administered by caudal vein injection 10 min prior to ischemia/reperfusion (I/R) injury. 24 h following I/R injury, ameliorated modified neurological severity scores (mNSS) and reduced infarct volume were observed in the PD treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Annexin V/propidium iodide assays demonstrated the anti-apoptotic effect of PD in the ischemic cortex. In addition, PD improved I/R injury-induced mitochondrial dysfunction, reflected by morphological observations and measurements of mitochondrial membrane potential and intracellular ATP measurement. Western blot analysis revealed an increase in B-cell lymphoma 2 apoptosis regulator (Bcl-2) expression, and a decrease in Bcl-2-associated protein X apoptosis regulator expression in the PD group in comparison with the vehicle treated group. PD treatment also prevented the release of cytochrome c from mitochondria into the cytoplasm, and blunted the activities of caspase-9 and caspase-3. Furthermore, PD treatment decreased the levels of reactive oxygen species in neurons isolated from the ischemic cortex. The findings of this study, therefore, suggest that PD has a dual effect, ameliorating both oxidative stress and mitochondria-dependent apoptosis, making it a promising new therapy for the treatment of ischemic stroke.