Park In H, Kim Mi K, Kim Seung U
Institute for Regenerative Medicine, Gachon University Gil Medical Center, 534-2 Yeonsu-dong, Inchon 406-799, Republic of Korea.
Biochem Biophys Res Commun. 2008 Dec 26;377(4):1025-30. doi: 10.1016/j.bbrc.2008.06.014. Epub 2008 Jun 17.
Ursodeoxycholic acid (UDCA), a component of bile acid, which is abundant in the gall bladder of bears, has been used in clinical medicine for cholestatic liver diseases. Recently, it was demonstrated that UDCA and its derivative tauroursodeoxycholic acid block apoptotic cell death in both hepatic and non-hepatic cells. Cisplatin, an effective anti-cancer drug, is known to cause sensory neuropathy in patients receiving the drug. In the present study, whether UDCA is effective in blocking cisplatin-induced cell death in mouse hybrid sensory neurons was conducted. N18D3 mouse hybrid sensory neurons exposed to cisplatin were found to undergo apoptotic cell death. Preincubation with UDCA completely blocked cisplatin-induced apoptotic cell death in the sensory neurons, and cisplatin-induced p53 accumulation was suppressed by UDCA treatment. These results indicate that UDCA has a neuroprotective effect on the cisplatin-induced neuronal cell death of sensory neurons via the downregulation of the p53 signaling pathway.
熊去氧胆酸（UDCA）是胆汁酸的一种成分，在熊的胆囊中含量丰富，已被用于临床医学治疗胆汁淤积性肝病。最近，有研究表明，UDCA及其衍生物牛磺熊去氧胆酸可阻止肝细胞和非肝细胞的凋亡性细胞死亡。顺铂是一种有效的抗癌药物，已知会使接受该药物治疗的患者出现感觉神经病变。在本研究中，我们探究了UDCA是否能有效阻止顺铂诱导的小鼠杂交感觉神经元细胞死亡。研究发现，暴露于顺铂的N18D3小鼠杂交感觉神经元会发生凋亡性细胞死亡。预先用UDCA孵育可完全阻止顺铂诱导的感觉神经元凋亡性细胞死亡，并且UDCA处理可抑制顺铂诱导的p53积累。这些结果表明，UDCA通过下调p53信号通路，对顺铂诱导的感觉神经元细胞死亡具有神经保护作用。
