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人重组粒细胞集落刺激因子对大鼠白消安诱导的睾丸损伤的影响。

Effect of human recombinant granulocyte colony-stimulating factor on rat busulfan-induced testis injury.

作者信息

Khanlarkhani Neda, Pasbakhsh Parichehr, Mortezaee Keywan, Naji Mohammad, Amidi Fardin, Najafi Atefeh, Sobhani Aligholi, Zendedel Adib

机构信息

Department of Anatomical Sciences, Tehran University of Medical Sciences, POB 14176-1351, Tehran, Iran.

Institute of Neuroanatomy, RWTH Aachen University, Aachen, Germany.

出版信息

J Mol Histol. 2016 Feb;47(1):59-67. doi: 10.1007/s10735-015-9647-y. Epub 2015 Dec 29.

Abstract

Granulocyte colony-stimulating factor (G-CSF) is known for proliferation and anti-apoptotic activities. We aimed to use this growth factor in busulfan-injured testis. 32 male Wistar rats were injected with a double dosage of 15 ml/kg busulfan with 14 days interval. Administration of human recombinant G-CSF (100 µg/kg) subcutaneously was performed in two different time periods: 3 days before and 2 days after receiving busulfan, G-CSF1; and at days 14-18 of busulfan injection, G-CSF2. Animals were sacrificed at the end of week five. Histological analysis, testis weight and sperm parameters (sperm count and viability) has been checked. Expressions of DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 (DDX4), deleted in azoospermia like (DAZL), transition protein 2 (TP2), proliferating cell nuclear antigen (PCNA) and 5-Bromo-20-deoxyuridine (BrdU) were assessed. Empty seminiferous tubules were apparent in the busulfan- and G-CSF2-injected rats, but not in the G-CSF1 group. The G-CSF1-treated animals showed an increase in testis weight and sperm count and viability along with high expressions of DDX4, DAZL, TP2, PCNA and BrdU; even so, the changes were reversed in the busulfan and G-CSF2 groups (for all p < 0.05). Our results revealed that G-CSF application prior to busulfan insult is a promising approach in fertility maintenance.

摘要

粒细胞集落刺激因子(G-CSF)以其增殖和抗凋亡活性而闻名。我们旨在将这种生长因子用于白消安损伤的睾丸。32只雄性Wistar大鼠每隔14天注射双倍剂量(15 ml/kg)的白消安。在两个不同时间段皮下注射人重组G-CSF(100 µg/kg):在接受白消安前3天和后2天,即G-CSF1组;在白消安注射的第14 - 18天,即G-CSF2组。在第五周结束时处死动物。检查了组织学分析、睾丸重量和精子参数(精子计数和活力)。评估了DEAD(天冬氨酸-谷氨酸-丙氨酸-天冬氨酸)盒多肽4(DDX4)、无精子症缺失样蛋白(DAZL)、过渡蛋白2(TP2)、增殖细胞核抗原(PCNA)和5-溴-2'-脱氧尿苷(BrdU)的表达。在注射白消安和G-CSF2的大鼠中可见空的生精小管,但在G-CSF1组中未出现。G-CSF1处理的动物睾丸重量、精子计数和活力增加,同时DDX4、DAZL、TP2、PCNA和BrdU表达升高;即便如此,在白消安和G-CSF2组中这些变化出现了逆转(所有p < 0.05)。我们的结果表明,在白消安损伤前应用G-CSF是一种有前景的维持生育力的方法。

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