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精原干细胞对阿霉素诱导的大鼠睾丸毒性的抗凋亡作用。

Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats.

作者信息

Mohamed Rasha H, Karam Rehab A, Hagrass Hoda A, Amer Mona G, Abd El-Haleem Manal R

机构信息

Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Gene. 2015 Apr 25;561(1):107-14. doi: 10.1016/j.gene.2015.02.015. Epub 2015 Feb 11.

Abstract

The present study was designed to investigate whether spermatogonial stem cells (SSCs) have possible effect on doxorubicin (DOX)-induced testicular apoptosis and damaged oxidant/antioxidant balance in rats. Sixty male Albino rats were divided into 3 groups: the saline control group, the testicular toxicity group (2mg/kg DOX once a week for 8 weeks) and the third group is a donor stem cells transplanted following pre-treatment with DOX. After the 8th week, the rats were sacrificed and tissues were collected and examined for CD95, CD95L, Caspase 3, and Caspase 8 gene expression using RT-PCR. While malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) were determined using colorimetric kits. Biochemical, histopathological and PCR results showed improvement of the SSCs' group compared to the DOX-group. It was observed that spermatogonial stem cell affected DOX-induced activation of intrinsic apoptotic signaling pathway via preventing DOX-induced increases in CD95 and CD95L levels as well as cleaved Caspase-8 and Caspase-3 levels in testicular tissues, however, spermatogonial stem cell decreased Dox-induced NF-κB activation as well. It can be concluded that SSCs may be utilized to develop new cell-based therapies, and to advance germline gene therapy.

摘要

本研究旨在探讨精原干细胞(SSCs)是否对阿霉素(DOX)诱导的大鼠睾丸细胞凋亡以及氧化/抗氧化平衡受损具有潜在影响。60只雄性白化大鼠被分为3组:生理盐水对照组、睾丸毒性组(每周一次给予2mg/kg DOX,共8周)以及第三组,即经DOX预处理后进行供体干细胞移植的组。第8周后,处死大鼠并收集组织,使用逆转录聚合酶链反应(RT-PCR)检测CD95、CD95L、半胱天冬酶3(Caspase 3)和半胱天冬酶8(Caspase 8)基因表达。同时,使用比色试剂盒测定丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)。生化、组织病理学和PCR结果显示,与DOX组相比,SSCs组有所改善。观察到精原干细胞通过防止DOX诱导的睾丸组织中CD95和CD95L水平以及裂解的Caspase-8和Caspase-3水平升高,影响DOX诱导的内源性凋亡信号通路的激活,然而,精原干细胞也降低了DOX诱导的核因子κB(NF-κB)激活。可以得出结论,SSCs可用于开发新的基于细胞的疗法,并推进生殖系基因治疗。

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