Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Nobakht M, Abdollahi A, Ghasemnejad-Berenji H, Mohajer Ansari J, Pashapour S, Dehpour A R
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Andrologia. 2018 Mar;50(2). doi: 10.1111/and.12846. Epub 2017 Jul 21.
The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.
本研究旨在评估二甲双胍对大鼠睾丸缺血/再灌注(I/R)损伤模型中细胞凋亡和附睾精子质量的影响。总共72只雄性大鼠被分为四组(每组n = 18):第1组(假手术组)、第2组(二甲双胍组)、第3组(扭转/去扭转 [T/D]+生理盐水)和第4组(T/D + 300 mg/kg二甲双胍)。通过将右侧睾丸顺时针旋转720°持续1小时来实现睾丸扭转。与假手术组相比,去扭转4小时后,组织丙二醛(MDA)水平和半胱天冬酶-3活性升高,而过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性降低(p <.001)。去扭转24小时后,在每组的6只大鼠中,通过测量生精小管直径平均值(MSTD)和TUNEL试验发现,组织病理学变化和生殖细胞凋亡显著恶化。此外,T/D后30天,检测每组6只动物的精子浓度和活力。二甲双胍预处理可降低去扭转4小时后的MDA和半胱天冬酶-3水平,并使抗氧化酶活性恢复正常,生殖细胞凋亡显著减少,MSTD以及精子功能显著改善。氧化应激和细胞凋亡的降低可能在二甲双胍的细胞保护作用中起主要作用。