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曲普瑞林对短期暴露于环磷酰胺的雄性白化大鼠海马和大脑皮质神经细胞保护作用的组织病理学和免疫组织化学研究

Histopathological and immunohistochemical study of the protective effect of triptorelin on the neurocytes of the hippocampus and the cerebral cortex of male albino rats after short-term exposure to cyclophosphamide.

作者信息

Shaibah Hassan S, Elsify Abd-Elhamid K, Medhat Taha M, Rezk Hassan M, El-Sherbiny Mohamed

机构信息

Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.

Department of Anatomy, Batterjee Medical College, Jeddah, Saudi Arabia.

出版信息

J Microsc Ultrastruct. 2016 Jul-Sep;4(3):123-132. doi: 10.1016/j.jmau.2015.12.002. Epub 2015 Dec 15.

Abstract

Chemotherapy treats many types of cancer effectively but it often causes side effects. Chemotherapy works on active cells, such as cancer cells, and some healthy cells. Side effects happen when chemotherapy damages these healthy cells. Today, many more drugs are available to treat side effects than in the past. Triptorelin (Decapeptyl) is a gonadotropin-releasing hormone agonist that is reported to have many therapeutic effects besides being an anti-cancer agent. In the current study, intraperitoneal cyclophosphamide (65 mg/kg/day) was administered for 4 weeks to induce marked dystrophic changes in the cerebral cortex and hippocampus of male albino rats. After 4 weeks, we observed significant degeneration of neurocytes with dystrophic changes. Subcutaneous triptorelin (0.05 mg/kg/day) for 4 weeks significantly improved histological signs of degeneration and apoptosis. Anti-Bcl2 staining of sections of the cerebral cortex and hippocampus showed that the apoptotic index was increased. This finding was confirmed by the anti-p53 staining, which showed a significant decrease in the apoptotic index. Ultimately, such improvements were accompanied by significant restoration of normal brain histology, as revealed by hematoxylin and eosin. In conclusion, triptorelin can reverse the apoptotic changes induced by cyclophosphamide therapy, which is more marked in the hippocampus than cerebral cortex.

摘要

化疗能有效治疗多种类型的癌症,但它常常会引发副作用。化疗作用于活跃细胞,如癌细胞和一些健康细胞。当化疗损害这些健康细胞时,副作用就会出现。如今,相较于过去,有更多药物可用于治疗副作用。曲普瑞林(德普佳)是一种促性腺激素释放激素激动剂,据报道,除了作为抗癌药物外,它还有许多治疗作用。在当前的研究中,对雄性白化大鼠腹腔注射环磷酰胺(65毫克/千克/天),持续4周,以诱导大脑皮层和海马体出现明显的营养不良性变化。4周后,我们观察到神经细胞出现显著退化并伴有营养不良性变化。皮下注射曲普瑞林(0.05毫克/千克/天),持续4周,显著改善了退化和凋亡的组织学迹象。大脑皮层和海马体切片的抗Bcl2染色显示凋亡指数增加。抗p53染色证实了这一发现,其显示凋亡指数显著降低。最终,苏木精和伊红染色显示,这些改善伴随着正常脑组织学的显著恢复。总之,曲普瑞林可以逆转环磷酰胺治疗所诱导的凋亡变化,这种变化在海马体中比在大脑皮层中更为明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d19/6014199/8a4698e10e15/JMAU-4-123-g001.jpg

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