即早基因c-Jun在顺铂诱发豚鼠耳蜗Corti器细胞凋亡中的作用

The Role of C-Jun Associated with in Cisplatin(CDDP) Apoptosis in Guinea Pig Cochlea

邢奋丽;邓毅;王林娥;曹克利;

1:南京医科大学附属南京第一医院耳鼻咽喉科

2:首都医科大学附属北京友谊医院耳鼻咽喉科

3:中国协和医科大学中国医学科学院北京协和医院耳鼻咽喉科

摘要
目的探讨即早基因c-Jun在耳蜗细胞凋亡中的作用。方法 20只豚鼠随机分为实验组和对照组,每组10只,实验组豚鼠腹腔注射顺铂4mg.kg-1.d-1,连续4天,制备感音神经性聋动物模型,对照组每天腹腔注射等量生理盐水。两组动物耳蜗组织切片后,用HE染色、末端转移酶介导的原位缺口末端标记染色(TUNEL)技术及电镜等观察耳蜗Corti器细胞凋亡状况,用免疫组化染色方法检测正常和凋亡耳蜗Corti器细胞的c-Jun表达情况。结果实验组豚鼠腹腔顺铂注射4天后,耳蜗Corti器的TUNEL阳性细胞数较对照组明显增多(P<0.05),实验组和对照组Corti器细胞c-Jun的平均光密度值分别为0.51±0.08和0.33±0.07,实验组c-Jun的表达高于对照组(P<0.05)。结论耳蜗细胞凋亡时c-Jun蛋白表达增加,表明c-Jun可能参与了耳蜗细胞凋亡的调控,是顺铂导致感音神经性聋的一个重要因素。
关键词
即早基因c-Jun;毛细胞;凋亡;顺铂;聋;感音神经性
基金项目(Foundation):
南京医科大学科技发展基金面上项目(08NMUM102)资助
作者
邢奋丽;邓毅;王林娥;曹克利;
参考文献

1 Greer JE,McGinn MJ,Povlishock JT.Diffuse traumatic ax-onal injury in the mouse induces atrophy,c-Jun activation,and axonal outgrowth in the axotomized neuronal population[J].J Neurosci,2011,31:5 089.

2赵晓鸿,陈照丽,赵守华,等.COX-2及其转录因子NFAT3和c-Fos在非小细胞肺癌中的表达及意义[J].中国肺癌杂志,2010,11:1 035.

3 Xu P,Das M,Reilly J,et al.JNK regulates FoxO-depen-dent autophagy in neurons[J].Genes Dev,2011,25:310.

4 Rybak LP.Mechanisms of cisplatin ototoxicity and progress in otoprotection[J].Curr Opin Otolaryngol Head Neck Surg,2007,15:364.

5 Ganm C,Holnmin S,Mathiesen T.Temporal profiles and cel-lular sources of three nitric oxide sythases isoforms in the brain after experimental contusion[J].Neurosurgery,2000,46:169.

6 Shalini S,Bansal MP.Co-operative effect of glutathione de-pletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro:insights to regulation of spermatogenesis[J].Biol Res,2007,40:307.

7许辉杰,黄魏宁.顺铂作用下沙鼠耳蜗螺旋神经节神经元和Corti器细胞的凋亡[J].中华耳鼻咽喉科杂志,2003,38:98.

8 Marek KW,Kurtz LM,Spitzer NC.c-Jun integrates calcium activity and tlx3expression to regulate neurotransmitter speci-fication[J].Nat Neurosci,2010,13:944.

9 Lefebvre P,Malgrange B,Lallemend F,et al.Mechanisms of cell death in the injured auditory system:otoprotective strate-gies[J].Audiol Neurotol,2002,7:165.

10 Martin LJ,Bergeron F,Viger RS,et al.Functional coopera-tion between GATA factors and c-Jun on the star promoter in MA-10leyclig cells[J].J Androl,2012,33:81.