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顺铂(CDDP)处理的豚鼠耳蜗中半胱天冬酶激活的脱氧核糖核酸酶(CAD)和半胱天冬酶3(CPP32)的表达

Expression of caspase-activated deoxyribonuclease (CAD) and caspase 3 (CPP32) in the cochlea of cisplatin (CDDP)-treated guinea pigs.

作者信息

Watanabe Ken-ichi, Inai Shunta, Jinnouchi Ken, Baba Shunkichi, Yagi Toshiaki

机构信息

Department of Oto-Rhino-Laryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Kawasaki, Tokyo 113-8603, Japan.

出版信息

Auris Nasus Larynx. 2003 Aug;30(3):219-25. doi: 10.1016/s0385-8146(03)00049-x.

Abstract

Cisplatin, an anti-cancer drug, is known to induce apoptosis. During apoptosis, double-stranded DNA is broken into single-stranded DNA by the action of caspases and caspase activated deoxyribonuclease (CAD). We immunohistochemically examined the cochlea of guinea pigs for signs of the apoptosis after the administration of cisplatin. Cisplatin (10 mg/kg b.w.) was intraperitoneally injected to guinea pigs and 3 days later, the animals were sacrificed by intracardiac perfusion of 4% paraformaldehyde. The temporal bones were then removed and immunohistochemically stained for CAD and caspase 3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling method. CAD was observed in the stria vascularis and the spiral ligament. Caspase 3 was also detected in the stria vascularis, the spiral ligament and the supporting cells of the organ of Corti. These findings suggest that apoptosis is involved in the cochlear damage observed in cancer patients treated with cisplatin.

摘要

顺铂是一种抗癌药物,已知其可诱导细胞凋亡。在细胞凋亡过程中,双链DNA在半胱天冬酶和半胱天冬酶激活的脱氧核糖核酸酶(CAD)的作用下被分解为单链DNA。我们通过免疫组织化学方法检查了给予顺铂后豚鼠耳蜗的细胞凋亡迹象。将顺铂(10mg/kg体重)腹腔注射给豚鼠,3天后,通过心脏灌注4%多聚甲醛处死动物。然后取出颞骨,使用末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记法对CAD和半胱天冬酶3进行免疫组织化学染色。在血管纹和螺旋韧带中观察到CAD。在血管纹、螺旋韧带和柯蒂氏器的支持细胞中也检测到半胱天冬酶3。这些发现表明,细胞凋亡与接受顺铂治疗的癌症患者中观察到的耳蜗损伤有关。

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