Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats
Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats
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DOI：
10.1007/s00726-010-0751-8
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发表时间：
2011-05
期刊：
影响因子：
3.5
通讯作者：
Mingxia Sun;Yi Gu;Yumei Zhao;Chao Xu
中科院分区：
文献类型：
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作者：
Mingxia Sun;Yi Gu;Yumei Zhao;Chao Xu
牛磺酸是神经系统中丰富的氨基酸，据报道以剂量依赖性方式减轻缺血性脑损伤。本研究旨在探讨牛磺酸是否通过影响脑梗死细胞死亡途径对脑卒中的保护作用。采用线栓法造成大鼠缺血2 h，再灌注22 h。再次证实，缺血后1小时静脉注射牛磺酸（50 mg/kg）可显著改善神经功能，并在再灌注后22小时缩小梗死体积。在溶剂处理的大鼠中，细胞内ATP水平以及半暗带和核心中的胞质和线粒体Bcl-xL水平显著降低，而核心中的胞质Bax水平以及半暗带和核心中的线粒体Bax水平显著增强。半暗带和核心区线粒体细胞色素C减少，胞浆细胞色素C增加。这些变化被牛磺酸逆转。此外，牛磺酸还能抑制钙蛋白酶和半胱天冬酶3的活化，减少α II-血影蛋白的降解，减轻半暗带和核心区的坏死和凋亡细胞死亡。这些数据表明，保护线粒体功能和阻断线粒体介导的细胞死亡途径可能是牛磺酸抗脑缺血作用的机制之一。
Taurine, an abundant amino acid in the nervous system, is reported to reduce ischemic brain injury in a dose-dependent manner. This study was designed to investigate whether taurine protected brain against experimental stroke through affecting mitochondria-mediated cell death pathway. Rats were subjected to 2-h ischemia by intraluminal filament, and then reperfused for 22 h. It was confirmed again that taurine (50 mg/kg) administered intravenously 1 h after ischemia markedly improved neurological function and decreased infarct volume at 22 h after reperfusion. In vehicle-treated rats, the levels of intracellular ATP and the levels of cytosolic and mitochondrial Bcl-xL in the penumbra and core were markedly reduced, while the levels of cytosolic Bax in the core and mitochondrial Bax in the penumbra and core were enhanced significantly. There was a decrease in cytochromeCin mitochondria and an increase in cytochromeCin the cytosol of the penumbra and core. These changes were reversed by taurine. Furthermore, taurine inhibited the activation of calpain and caspase-3, reduced the degradation of αII-spectrin, and attenuated the necrotic and apoptotic cell death in the penumbra and core. These data demonstrated that preserving the mitochondrial function and blocking the mitochondria-mediated cell death pathway may be one mechanism of taurine’s action against brain ischemia.