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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats
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Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats

机译：牛磺去氧胆酸减少大鼠急性出血性中风后的细胞凋亡并保护其免受神经损伤

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摘要

Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates cell death by interrupting classic pathways of apoptosis. Intracerebral hemorrhage (ICH) is a devastating acute neurological disorder, without effective treatment, in which a significant loss of neuronal cells is thought to occur by apoptosis. In this study, we evaluated whether TUDCA can reduce brain injury and improve neurological function after ICH in rats. Administration of TUDCA before or up to 6 h after stereotaxic collagenase injection into the striatum reduced lesion volumes at 2 days by as much as 50%. Apoptosis was ≈50% decreased in the area immediately surrounding the hematoma and was associated with a similar inhibition of caspase activity. These changes were also associated with improved neurobehavioral deficits as assessed by rotational asymmetry, limb placement, and stepping ability. Furthermore, TUDCA treatment modulated expression of certain Bcl-2 family members, as well as NF-κB activity. In addition to its protective action at the mitochondrial membrane, TUDCA also activated the Akt-1/protein kinase Bα survival pathway and induced Bad phosphorylation at Ser-136. In conclusion, reduction of brain injury underlies the wide-range neuroprotective effects of TUDCA after ICH. Thus, given its clinical safety, TUDCA may provide a potentially useful treatment in patients with hemorrhagic stroke and perhaps other acute brain injuries associated with cell death by apoptosis.
机译：牛磺去氧胆酸（TUDCA）是一种内源性胆汁酸，可通过中断经典的凋亡途径来调节细胞死亡。脑出血（ICH）是一种破坏性的急性神经系统疾病，没有进行有效的治疗，认为其中神经元细胞的大量丢失是由凋亡引起的。在这项研究中，我们评估了TUDCA是否可以减轻脑出血后大鼠的脑损伤并改善神经功能。在将立体定向胶原酶注射到纹状体之前或之后最多6小时施用TUDCA，可在2天时将病变体积减少多达50％。在血肿周围的区域，细胞凋亡减少了约50％，并与caspase活性的类似抑制有关。这些变化还与通过旋转不对称，肢体放置和踩踏能力评估的神经行为缺陷改善有关。此外，TUDCA处理可调节某些Bcl-2家族成员的表达以及NF-κB活性。除了对线粒体膜的保护作用外，TUDCA还激活了Akt-1 /蛋白激酶Bα的生存途径，并诱导Ser-136的Bad磷酸化。总之，减轻脑损伤是ICH后TUDCA广泛的神经保护作用的基础。因此，鉴于其临床安全性，TUDCA可能为出血性中风以及可能与细胞凋亡导致的细胞死亡相关的其他急性脑损伤患者提供潜在的有用治疗方法。

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