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桦褐孔菌多糖通过调节 Nrf2-PI3K/AKT 通路改善弓形虫感染引起的雄性小鼠生殖功能障碍。

Inonotus obliquus polysaccharide ameliorates impaired reproductive function caused by Toxoplasma gondii infection in male mice via regulating Nrf2-PI3K/AKT pathway.

机构信息

College of Pharmacy, Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.

Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR China.

出版信息

Int J Biol Macromol. 2020 May 15;151:449-458. doi: 10.1016/j.ijbiomac.2020.02.178. Epub 2020 Feb 18.

Abstract

This study was carried out to investigate the effects of Inonotus obliquus polysaccharide (IOP) on impaired reproductive function and its mechanisms in Toxoplasma gondii (T. gondii)-infected male mice. Results showed that IOP significantly improved the spermatogenic capacity and ameliorated pathological damage of testis, increased serum testosterone (T), luteinizing hormone (LH) and follicular-stimulating hormone (FSH) levels in T. gondii-infected male mice. IOP effectively up-regulated testicular steroidogenic acute regulatory protein (StAR), P450scc and 17β-HSD expressions. IOP also significantly decreased the levels of malondialdehyde (MDA) and nitric oxide (NO), but increased the activities of antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH). Furthermore, IOP up-regulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NADPH quinoneoxidoreductase-1 (NQO-1), and suppressed the apoptosis of testicular cells by decreasing Bcl-2 associated x protein (Bax) and cleaved caspase-3 expressions. IOP further enhanced testicular phosphatidylinositol 3-kinase (PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) expression levels. It demonstrates the beneficial effects of IOP on impaired reproductive function in T. gondii-infected male mice due to its anti-oxidative stress and anti-apoptosis via regulating Nrf2-PI3K/AKT signaling pathway.

摘要

本研究旨在探讨桦褐孔菌多糖(IOP)对弓形虫(T. gondii)感染雄性小鼠生殖功能障碍的影响及其机制。结果表明,IOP 可显著改善弓形虫感染雄性小鼠的生精能力和睾丸病理损伤,提高血清睾酮(T)、促黄体生成素(LH)和促卵泡生成素(FSH)水平。IOP 有效地上调睾丸甾体生成急性调节蛋白(StAR)、P450scc 和 17β-HSD 的表达。IOP 还显著降低丙二醛(MDA)和一氧化氮(NO)水平,增加抗氧化酶超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的活性。此外,IOP 通过下调 Bcl-2 相关 X 蛋白(Bax)和裂解半胱天冬酶-3(caspase-3)的表达,上调核因子红细胞 2 相关因子 2(Nrf2)、血红素加氧酶-1(HO-1)和 NADPH 醌氧化还原酶-1(NQO-1)的表达,抑制睾丸细胞凋亡。IOP 进一步增强了睾丸磷脂酰肌醇 3-激酶(PI3K)、磷酸蛋白激酶 B(p-AKT)和磷酸哺乳动物雷帕霉素靶蛋白(p-mTOR)的表达水平。这表明 IOP 通过调节 Nrf2-PI3K/AKT 信号通路发挥抗氧化应激和抗凋亡作用,对弓形虫感染雄性小鼠生殖功能障碍具有有益作用。

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