Mohamed Rasha H, Karam Rehab A, Hagrass Hoda A, Amer Mona G, Abd El-Haleem Manal R
Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Gene. 2015 Apr 25;561(1):107-14. doi: 10.1016/j.gene.2015.02.015. Epub 2015 Feb 11.
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.
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。
