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薯蓣皂苷元通过抑制细胞凋亡、氧化应激和炎症改善链脲佐菌素诱导的糖尿病大鼠睾丸损伤。

Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation.

机构信息

School of Medicine, Shahed University, Tehran, Iran.

Department of Anatomy and Pathology, School of Medicine, Shahed University, Tehran, Iran.

出版信息

Int Immunopharmacol. 2019 May;70:37-46. doi: 10.1016/j.intimp.2019.01.047. Epub 2019 Feb 19.

DOI:10.1016/j.intimp.2019.01.047
PMID:30785089
Abstract

Diabetes mellitus (DM) is a prevalent metabolic disorder that is associated with development of some complications in male reproductive system including testicular damage, sexual dysfunction, abnormal spermatogenesis, and infertility. Diosgenin is a natural steroidal saponin with anti-diabetic, anti-oxidative, and anti-inflammatory effects. This research study was undertaken to explore the protective effect of diosgenin against diabetes-induced testicular damage in the rat. Ten days following streptozotocin (STZ; i.p.), diosgenin was daily administered for 6 weeks (p.o.). Diosgenin administration to diabetic rats significantly improved body weight and lowered serum glucose. In addition, diosgenin-treated diabetic group had a significantly lower level of malondialdehyde (MDA), protein carbonyl, greater level of glutathione (GSH), and higher activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) in addition to testicular improvement of ferric reducing antioxidant power (FRAP). Furthermore, diosgenin significantly improved serum insulin and testosterone level and alleviated testicular markers of inflammation including tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) in diabetic rats. Moreover, apoptotic markers including caspase 3 activity, Annexin V, and DNA fragmentation decreased, mitochondrial membrane potential (MMP) accentuated, and myeloperoxidase (MPO) activity as a biomarker of neutrophil infiltration decreased in diosgenin-treated diabetic group. Additionally, diosgenin was capable to improve sperm count, motility, and viability in addition to prevention of damage to seminiferous tubules in diabetic animals. Collectively, diosgenin ameliorates testicular damage in DM, at least via partial suppression of apoptosis, oxidative stress, inflammation, and neutrophil infiltration and also via partial restoration of mitochondrial integrity.

摘要

糖尿病(DM)是一种常见的代谢紊乱疾病,与男性生殖系统的一些并发症有关,包括睾丸损伤、性功能障碍、异常精子发生和不育。薯蓣皂苷元是一种天然甾体皂甙,具有降血糖、抗氧化和抗炎作用。本研究旨在探讨薯蓣皂苷元对糖尿病大鼠睾丸损伤的保护作用。链脲佐菌素(STZ;腹腔注射)后 10 天,每天给予薯蓣皂苷元治疗 6 周(口服)。薯蓣皂苷元治疗糖尿病大鼠显著改善了体重,降低了血糖。此外,薯蓣皂苷元治疗的糖尿病组丙二醛(MDA)、蛋白羰基、谷胱甘肽(GSH)水平显著降低,超氧化物歧化酶(SOD)、过氧化氢酶和谷胱甘肽过氧化物酶(GPx)活性显著升高,同时还改善了糖尿病大鼠的铁还原抗氧化能力(FRAP)。此外,薯蓣皂苷元显著改善了糖尿病大鼠的血清胰岛素和睾酮水平,并缓解了睾丸炎症标志物,包括肿瘤坏死因子-α(TNFα)和白细胞介素 6(IL-6)。此外,凋亡标志物包括 caspase 3 活性、Annexin V 和 DNA 片段减少,线粒体膜电位(MMP)增强,髓过氧化物酶(MPO)活性作为中性粒细胞浸润的生物标志物减少。此外,薯蓣皂苷元能够改善糖尿病动物的精子计数、活力和存活率,并防止曲细精管损伤。总之,薯蓣皂苷元可改善 DM 中的睾丸损伤,至少部分通过抑制细胞凋亡、氧化应激、炎症和中性粒细胞浸润,并部分通过恢复线粒体完整性。

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