Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Stem Cell Res Ther. 2021 Jun 29;12(1):370. doi: 10.1186/s13287-021-02439-x.
This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.
Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 10 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001).
Mel-ADMSCs effectively protected the testis against TTIR injury.
本研究旨在验证联合褪黑素（Mel）和脂肪间充质干细胞（ADMSCs）治疗在保护睾丸免受急性睾丸扭转致缺血再灌注（TTIR）损伤方面优于单一治疗的假说。
雄性成年 SD 大鼠（n = 30）等分为 5 组：1 组（假手术对照）、2 组（TTIR/右侧/左侧睾丸扭转，即缺血 2 h，然后逆时针旋转 720°至初始位置，再灌注 72 h）、3 组（TTIR + Mel/腹腔内给药/缺血后 30 min 给予 50 mg/kg，然后 TTIR 后 3 h 和第 1/2/3 天给予 20 mg/kg）、4 组（TTIR + ADMSCs/缺血后 30 min 尾静脉注射 1.2×10 个细胞/个，然后 TTIR 后第 1/2 天）和 5 组（TTIR + Mel + ADMSCs/尾静脉注射）。结果显示，氧化应激（NOX-1/NOX-2/氧化蛋白）、凋亡/线粒体损伤（线粒体 Bax/裂解 caspase3/裂解 PARP/胞质细胞色素 C）和纤维化（TGF-β/Smad3）生物标志物的蛋白表达以及睾丸损伤评分在 1 组最低，在 2 组最高，在 3 组和 4 组显著高于 5 组，但在 3 组和 4 组之间无差异，而雄激素受体（AR）和波形蛋白的蛋白表达与氧化应激呈相反模式（均 p < 0.0001）。炎症细胞水平（MMP-9/MPO/CD68）呈现相同模式，而各组 Sertoli 细胞、α-微管蛋白、AR 和波形蛋白以及生精小管厚度呈现相反的氧化应激模式（均 p < 0.0001）。
Mel-ADMSCs 可有效保护睾丸免受 TTIR 损伤。
