Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway.
Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway.
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Tetramethylpyrazine 通过影响线粒体依赖性 Caspase-3 凋亡途径来预防实验性蛛网膜下腔出血后的早期脑损伤。
DOI：
10.1155/2017/3514914
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Hang C
中科院分区：
文献类型：
--
作者：
Li S;Xiao X;Ni X;Ye Z;Zhao J;Hang C
本研究旨在验证川芎嗪(TMP)通过影响线粒体依赖的caspase-3凋亡通路对蛛网膜下腔出血(SAH)后早期脑损伤的保护作用。TMP在大鼠交叉前蛛网膜下腔出血模型后给药。观察动物神经行为功能，测定脑组织线粒体形态、线粒体和胞浆钙离子含量以及线粒体膜电位变化(Δψm)。检测胞浆细胞色素c(Cytc)、线粒体衍生的第二型半胱氨酸天冬氨酸氨基转移酶激活剂(Smac)和裂解型caspase-3B细胞淋巴瘤2(Bcl2)在细胞中的表达，并检测细胞凋亡情况。与生理盐水相比，TMP治疗导致较少的细胞凋亡和较轻的线粒体损伤，并有可能在神经行为结果方面表现得更好。TMP还能改善线粒体和胞浆内钙超载，减轻Δψm的下降，并抑制胞浆Cytc、Smac的表达，使Caspase3断裂，但上调bcl2的表达。提示TMP在SAH大鼠模型中具有抗细胞凋亡的作用，其机制可能与线粒体钙超载引起的caspase-3凋亡途径有关。这一发现为SAH后早期脑损伤提供了新的治疗方案。
This study was to test the hypothesis that tetramethylpyrazine (TMP) protected against early brain injury after subarachnoid hemorrhage (SAH) by affecting the mitochondrial-dependent caspase-3 apoptotic pathway. TMP was administrated after the rats' prechiasmatic SAH mode. Animal neurobehavioral functions were assessed and the mitochondrial morphology, mitochondrial and cytoplasmic calcium, and mitochondrial membrane potential changes (Δψm) of the brain tissues were measured. The expressions of cytoplasmic cytochrome c (cyt c), second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3 B-cell lymphoma 2 (bcl-2) in cells were determined and cellular apoptosis was detected. The treatment of TMP resulted in less apoptotic cells and milder mitochondrial injury and potentially performed better in the neurobehavioral outcome compared to those with saline. Also, TMP ameliorated calcium overload in mitochondria and cytoplasm and alleviated the decrease of Δψm. In addition, TMP inhibited the expression of cytoplasmic cyt c, Smac, and cleaved caspase-3, yet it upregulated the expression of bcl-2. These findings suggest that TMP exerts an antiapoptosis property in the SAH rat model and this is probably mediated by the caspase-3 apoptotic pathway triggered by mitochondrial calcium overload. The finding offers a new therapeutic candidate for early brain injury after SAH.