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长春碱和长春新碱对大鼠精子发生的早期影响:采用一种新的透照相差显微镜法进行分析

Early effects of vinblastine and vincristine on the rat spermatogenesis: analyses by a new transillumination-phase contrast microscopic method.

作者信息

Parvinen L M, Söderström K O, Parvinen M

出版信息

Exp Pathol (Jena). 1978;15(2):85-96. doi: 10.1016/s0014-4908(78)80072-6.

Abstract

Male sterility belongs to the recently recognized complications of cancer chemotherapy and has an increasing importance. Therefore, more information about the mode of action of anticancer drugs on mammalian spermatogenesis is needed. We have developed a technique based on transillumination of living, freshly isolated unstained rat seminiferous tubules, where the cells specifically killed by the drugs are recognized as dull zones. Early stages of cell degeneration can be rapidly analyzed by phase contrast microscopy of living cells. Because the transillumination technique, in addition, permits an accurate recognition of the segments of the seminiferous epithelial wave, the cells representing various stages of the mitotic and meiotic cell cycles during spermatogenesis can be isolated in living state for morphological analysis. Vinblastine and vincristine cause an arrest of mitotic and meiotic divisions to metaphase followed by cell death, which was more rapid after vincristine administration. Both alkaloids had a slight damaging effect on the pachytene spermatocytes. Large doses of both drugs primarily affected the Sertoli cells by destroying their microtubules and mitochondria. Vincristine specifically damaged the acrosomic system and the cytoplasmic bridges of the young spermatids.

摘要

男性不育属于近期才被认识到的癌症化疗并发症,且其重要性日益增加。因此,需要更多关于抗癌药物对哺乳动物精子发生作用方式的信息。我们开发了一种基于对新鲜分离的未染色活大鼠生精小管进行透照的技术,其中被药物特异性杀死的细胞被识别为暗区。细胞变性的早期阶段可通过对活细胞的相差显微镜快速分析。此外,由于透照技术能够准确识别生精上皮波的节段,因此在生精过程中代表有丝分裂和减数分裂细胞周期不同阶段的细胞可以在活状态下分离出来进行形态学分析。长春碱和长春新碱会使有丝分裂和减数分裂停滞在中期,随后细胞死亡,长春新碱给药后细胞死亡更快。这两种生物碱对粗线期精母细胞都有轻微的损伤作用。大剂量的这两种药物主要通过破坏支持细胞的微管和线粒体来影响支持细胞。长春新碱特异性地损伤了年轻精子细胞的顶体系统和细胞质桥。

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