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虫草素减轻 HO 暴露的 Leydig 细胞中的生精和氧化还原相关表达,并调节老龄大鼠睾丸氧化凋亡信号通路。

Cordycepin mitigates spermatogenic and redox related expression in HO-exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats.

机构信息

Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.

Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.

出版信息

Pharm Biol. 2022 Dec;60(1):404-416. doi: 10.1080/13880209.2022.2033275.

Abstract

CONTEXT

Cordycepin (COR), from L., (Cordycipitaceae), is a valuable agent with immense health benefits.

OBJECTIVE

The protective effects of COR in ageing-associated oxidative and apoptosis events and hydrogen peroxide (HO)-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated.

MATERIALS AND METHODS

Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR.

RESULTS

COR treatment (1, 5, and 10 μg/mL) significantly ( 0.05 ∼  0.001) inhibited the HO-induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione--transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in HO-exposed TM3 cells were significantly ( 0.05 ∼  0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly ( 0.05).

CONCLUSION

COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.

摘要

背景

蛹虫草(COR)是一种来自于(虫草属)的有价值的物质,具有巨大的健康益处。

目的

本研究旨在探讨 COR 对衰老相关氧化应激和凋亡事件以及过氧化氢(HO)暴露导致 TM3 间质细胞生殖基因改变的保护作用。

材料和方法

雄性 Sprague-Dawley 大鼠分为青年对照组(YC)、老年对照组(AC)和 COR 处理组(COR-20)。COR-20 组每天给予 COR(20mg/kg),连续 6 个月。用 MTT[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐]和酶联免疫试剂盒分析细胞活力和激素水平,用 1、5 和 10μg/mL 的 COR 进行处理。通过 Western blot 和实时 RT-PCR 评估睾丸组织中氧化酶、生殖和凋亡表达。

结果

COR 处理(1、5 和 10μg/mL)显著(P<0.05~0.001)抑制了 HO 诱导的活细胞百分比下降(从 63.27%增加到 71.25%、85.67%和 93.97%),并降低了丙二醛(MDA)含量(从 4.28 减少到 3.98、3.14 和 1.78nM MDA/mg 蛋白)。此外,COR 还显著改善了 HO 暴露的 TM3 细胞中降低的抗氧化酶(谷胱甘肽 S-转移酶 mu5、谷胱甘肽过氧化物酶 4 和过氧化物还原酶 3)、生殖相关因子(神经连接蛋白-2 和抑制素-α)和睾酮水平。在老年大鼠中,COR(20mg/kg)恢复了改变的酶和非酶抗氧化状态,并显著降低了 p53 和 Bax/Bcl-2 表达的凋亡(P<0.05)。

结论

COR 可能被开发为一种潜在的对抗衰老相关和氧化应激诱导的男性不育的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/915f/8863333/6de667071493/IPHB_A_2033275_F0001_B.jpg

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