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百里香提取物可通过抑制氧化损伤和增加胰岛素受体底物和丙酮酸激酶在大鼠精子中的表达来克服糖尿病引起的生殖功能障碍。

Thyme extract could overcome diabetes-induced reproductive dysfunction by inhibiting oxidative damage and increasing the expression of insulin receptor substrate and pyruvate kinase in the rat sperm.

机构信息

Department of Basic Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.

Department of Animal Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.

出版信息

J Pharm Pharmacol. 2024 May 3;76(5):534-544. doi: 10.1093/jpp/rgad099.

Abstract

OBJECTIVES

Oxidative stress and disruption of energy metabolism in the reproductive system, especially sperm, play a significant role in diabetes-related infertility. Zataria multiflora Boissis (ZMB), a medicinal plant containing various bioactive compounds, may have efficacy in treating metabolic diseases and reproductive disorders. Therefore, the aim of this study was to investigate the effects of different doses of ZMB extract on diabetes-induced reproductive dysfunction by assessing oxidative damage and the gene expression of insulin receptor substrate (IRS) and pyruvate kinase (PK) in male rats' sperm.

METHODS

Sixty adult male Wistar rats were randomly divided into six groups; control (C), diabetes (D), and diabetic animals treated with glibenclamide (G, 50 mg/kg) and thyme extract (T100, T200, and T400). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ) (50 mg/kg). Insulin, glucose, oxidative and pro-inflammatory markers in the serum, and gene expressions of IRS, and PK were measured in the stored sperms in the epididymis. Changes in the process of spermatogenesis were assessed through the histological evaluation of the testis. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the quantity and quality of thyme extract.

KEY FINDINGS

The study results indicated that body weight, food intake, and sperm parameters significantly improved in a dose-dependent manner in the T200 group compared to the other groups. Additionally, in the same group, pro-inflammatory biomarkers, DNA fragmentation, and MDA levels decreased, while the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes in the stored epididymal sperm significantly improved compared to the other groups. The expression of IRS and PK, along with the mean counts of spermatogenesis cell lines (especially Sertoli cells), significantly increased in the T200 group.

SUMMARY

In conclusion, thymol appears to alleviate diabetes-induced reproductive dysfunction by inhibiting oxidative damage, improving the metabolic state, and upregulating the expression of IRS and PK genes in the sperm of male rats.

摘要

目的

氧化应激和能量代谢紊乱在生殖系统中,特别是精子中,在糖尿病相关不孕中起着重要作用。香薄荷(ZMB)是一种含有多种生物活性化合物的药用植物,可能对治疗代谢疾病和生殖障碍有效。因此,本研究旨在通过评估雄性大鼠精子的氧化损伤和胰岛素受体底物(IRS)和丙酮酸激酶(PK)基因的表达,研究不同剂量的 ZMB 提取物对糖尿病引起的生殖功能障碍的影响。

方法

将 60 只成年雄性 Wistar 大鼠随机分为 6 组;对照组(C)、糖尿病组(D)和糖尿病动物用格列本脲(G,50mg/kg)和百里香提取物(T100、T200 和 T400)治疗。通过腹腔注射链脲佐菌素(STZ)(50mg/kg)诱导糖尿病。测量血清中的胰岛素、葡萄糖、氧化和促炎标志物,以及储存的附睾精子中的 IRS 和 PK 基因表达。通过睾丸组织学评估评估精子发生过程的变化。使用气相色谱-质谱联用(GC-MS)分析百里香提取物的数量和质量。

主要发现

研究结果表明,与其他组相比,T200 组的体重、食物摄入量和精子参数均呈剂量依赖性显著改善。此外,在同一组中,促炎生物标志物、DNA 片段化和 MDA 水平降低,而储存的附睾精子中的 CAT、SOD 和 GPx 酶水平显著改善,与其他组相比。T200 组 IRS 和 PK 的表达以及精原细胞系的平均计数(特别是支持细胞)显著增加。

结论

总之,百里香酚通过抑制氧化损伤、改善代谢状态以及上调雄性大鼠精子中 IRS 和 PK 基因的表达,缓解糖尿病引起的生殖功能障碍。

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