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蜂胶提取物纳米颗粒可缓解糖尿病诱导的雄性大鼠生殖功能障碍:抗糖尿病、抗氧化及类固醇生成调节作用

Propolis extract nanoparticles alleviate diabetes-induced reproductive dysfunction in male rats: antidiabetic, antioxidant, and steroidogenesis modulatory role.

作者信息

Emil Abram B, Hassan Neven H, Ibrahim Sally, Hassanen Eman I, Eldin Zienab E, Ali Sara E

机构信息

Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

Department of Animal Reproduction and AI, Veterinary Research Institute, National Research Centre, Dokki, Giza, 12622, Egypt.

出版信息

Sci Rep. 2024 Dec 23;14(1):30607. doi: 10.1038/s41598-024-81949-z.

DOI:10.1038/s41598-024-81949-z
PMID:39715797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11666763/
Abstract

Diabetes can affect male fertility via oxidative stress and endocrine system disruption. Nanomedicine based on natural products is employed to address diabetes complications. The current study aims to investigate the potential beneficial effect of propolis extract nanoparticles against diabetes-induced testicular damage in male rats. Sixty male rats were randomly allocated to six groups (n = 10). The first group served as a control group. The second and third received propolis extract (Pr) and propolis extract nanoparticles (PrNPs). The fourth group is the diabetic group that received streptozotocin (STZ) (55 mg kg/bwt) single-dose i/p. The fifth and sixth groups are diabetic rats treated with Pr and PrNPs. Both Pr and PrNPs were received at a dose (100 mg/kg bwt) orally. After 60 days, animals were euthanized, then pancreatic and testicular tissues were collected for redox status evaluation, gene expression analysis, and histopathological examination. Also, hormonal analysis (Insulin, total testosterone, and luteinizing hormone (LH) ) along with semen quality evaluation were done. Results showed that the induction of diabetes led to testicular and pancreatic redox status deterioration showing a reduction in reduced glutathione (GSH) as well as elevation of malondialdehyde (MDA), and nitric oxide (NO) levels. Also, relative transcript levels of testicular cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 3β-Hydroxysteroid dehydrogenase (HSD-3β), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) were significantly down-regulated, While the advanced glycation end-product receptor (AGER) relative gene expression was significantly upregulated. Furthermore, hormonal and semen analysis disturbances were observed. Upon treatment with Pr and PrNPs,  a marked upregulation of testicular gene expression of CYP11A1, HSD-3β, and NFE2L2 as well as a downregulation of AGER, was observed. Hormones and semen analysis were improved. In addition, the testicular and pancreatic redox status was enhanced. Results were confirmed via histopathological investigations. PrNPs outperformed Pr in terms of steroidogenesis pathway improvement, testicular antioxidant defense mechanism augmentation, and prospective antidiabetic activity.

摘要

糖尿病可通过氧化应激和内分泌系统紊乱影响男性生育能力。基于天然产物的纳米医学被用于解决糖尿病并发症。本研究旨在探讨蜂胶提取物纳米颗粒对糖尿病诱导的雄性大鼠睾丸损伤的潜在有益作用。60只雄性大鼠被随机分为6组(n = 10)。第一组作为对照组。第二组和第三组分别接受蜂胶提取物(Pr)和蜂胶提取物纳米颗粒(PrNPs)。第四组是接受链脲佐菌素(STZ)(55 mg/kg体重)腹腔注射单剂量的糖尿病组。第五组和第六组是用Pr和PrNPs治疗的糖尿病大鼠。Pr和PrNPs均以口服剂量(100 mg/kg体重)给药。60天后,对动物实施安乐死,然后收集胰腺和睾丸组织进行氧化还原状态评估、基因表达分析和组织病理学检查。此外,还进行了激素分析(胰岛素、总睾酮和促黄体生成素(LH))以及精液质量评估。结果表明,糖尿病的诱导导致睾丸和胰腺氧化还原状态恶化,表现为还原型谷胱甘肽(GSH)减少以及丙二醛(MDA)和一氧化氮(NO)水平升高。此外,睾丸细胞色素P450家族11亚家族A成员1(CYP11A1)、3β-羟基类固醇脱氢酶(HSD-3β)和核因子(红细胞衍生2)样2(NFE2L2)的相对转录水平显著下调,而晚期糖基化终产物受体(AGER)的相对基因表达显著上调。此外,还观察到激素和精液分析紊乱。在用Pr和PrNPs治疗后,观察到睾丸CYP11A1、HSD-3β和NFE2L2基因表达明显上调,而AGER下调。激素和精液分析得到改善。此外,睾丸和胰腺的氧化还原状态得到增强。组织病理学研究证实了结果。在改善类固醇生成途径、增强睾丸抗氧化防御机制和潜在抗糖尿病活性方面,PrNPs优于Pr。

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