Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Department of Neurology, Ninghai People's Hospital, Ninghai, 315600, China.
Biol Res. 2020 Dec 1;53(1):56. doi: 10.1186/s40659-020-00323-1.
Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH.
Sprague-Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated.
TUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA.
Our findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.
神经元凋亡在蛛网膜下腔出血（SAH）后早期脑损伤的发病机制中起着关键作用。本研究探讨了牛磺熊去氧胆酸（TUDCA）在减轻 SAH 后神经元凋亡中的作用及其潜在机制。
将 Sprague-Dawley 大鼠制成 SAH 模型，并通过颈内动脉注射 TUDCA。在 SAH 前 48 小时通过侧脑室注射小干扰 RNA（siRNA）用于 TGR5。评估神经功能评分、脑水含量、Western blot、TUNEL 染色和免疫荧光染色。
TUDCA 可减轻 SAH 后 24 小时和 72 小时的脑水含量和改善神经功能评分。TUDCA 给药可防止 SIRT3 和 BCL-2 表达减少以及 BAX 和 cleaved caspase-3 表达增加。SAH 后内源性 TGR5 表达上调，用 TGR5 siRNA 处理后加重了 SAH 后的神经功能结果，并且 TGR5 siRNA 也消除了 TUDCA 在 SAH 后 24 小时的保护作用。
我们的研究结果表明，TUDCA 可以通过 TGR5/SIRT3 信号通路减轻 SAH 后神经元凋亡并改善神经功能。TUDCA 可能是 SAH 抗细胞凋亡治疗的有吸引力的候选药物。
