Fas和caspase-8信号通路在外周听觉系统老化中的作用和机制研究

The Roles and Mechanism of Fas and caspase-8 Signal Transduction Pathway in Cochlea in Response to Aging

罗凌惠;龚树生;

1:华中科技大学同济医学院附属协和医院耳鼻咽喉科

2:首都医科大学附属北京同仁医院耳鼻咽喉-头颈外科

摘要
目的检测老年大鼠耳蜗Fas受体及caspase-8 mRNA表达水平变化,研究细胞死亡受体途径在外周听觉系统老化中的作用和机制。方法以老年Wistar大白鼠(2022月龄)及成年Wistar大白鼠(222月龄)及成年Wistar大白鼠(23月龄)各10只为实验对象,采用半定量逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)的方法检测耳蜗组织Fas受体及caspase-8基因mRNA的含量。结果老年组耳蜗组织Fas受体及caspase-8mRNA的表达水平均高于成年组,差异均有显著统计学意义(P<0.01)。结论老年大鼠耳蜗Fas及caspase-8表达明显升高,说明耳蜗的老化与fas途径的凋亡密切相关;Fas及caspase-8信号通路增强可能在老年性聋发病机制中有重要作用。
关键词
Fas受体;Caspase-8基因;耳蜗;老化;半定量逆转录聚合酶链反应
基金项目(Foundation):
国家自然科学基金资助项目(30471879);; 高校青年教师奖;; 湖北省卫生厅科研基金资助项目(JXIBO56)
作者
罗凌惠;龚树生;
参考文献

1 Usami S,Takumi Y,Fujita S.Cell death in the inner ear as-sociated with aging is apoptosis[J].Brain Res,1997,747:147.

2 Zheng Y,Ikeda K,Nakamura M,et al.Endonuclease cleav-age of DNA in the aged cochlea of Mongolian gerbil[J].HearRes,1998,126:11.

3 Morishita H,Makishima T,Kaneko C,et al.Deafness due todegeneration of cochlear neurons in caspase-3-deficient mice[J].Biochem Biophys Res Commun,2001,284:142.

4 Krantic S,Mechawar N,Reix S,et al.Molecular basis ofprogrammed cell death involved in neurodegeneration[J].Trends Neurosci,2005,28:670.

5杨燕珍,龚树生,余青松,等.高血压对大鼠听功能及耳蜗乳酸脱氢酶、胆碱酯酶影响的研究[J].中华老年医学杂志,2003,12:30.

6 Zhang Y,Chong E,Herman B.Age-associated increases inthe activity of multiple caspases in Fisher 344 rat organs[J].Exp Gerontol,2002,37:777.

7许丽娟,龚树生,汪吉宝,等.内耳免疫反应中细胞凋亡的研究[J].中华耳鼻咽喉科杂志,2005,39:668.

8 Matsui JI,Cotanche DA.Sensory hair cell death and regenera-tion:two halves of the same equation[J].Curr Opin Otolar-yngol Head Neck Surg,2004,12:418.

9 Pistilli EE,Jackson JR,Alway SE.Death receptor-associatedpro-apoptotic signaling in aged skeletal muscle[J].Apopto-sis,2006,11:2 115.

10 A1gecriras-Schimnich A,Barnhart BC,Peter E.Apoptosis-independent functions of killer caspases[J].Curr Opin CellBiol,2002,14:721.

11 Gervais FG,Singaja R,Xanthoudakis S,et al.Recruitmentand activation of caspase-8 by the Huntingtin-interactingprotein Hip-1 and a novel partner Hippi[J].Nat Cell Biol,2002,4:95.