Graduate School of Hebei Medical University, Shijiazhuang, 050017, China.
Department of College of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang, 050024, China.
Biol Trace Elem Res. 2024 Nov;202(11):5081-5093. doi: 10.1007/s12011-023-04054-8. Epub 2024 Jan 8.
The long-term use of tripterygium glycosides (TG) can lead to male reproductive damage. Research indicates that zinc and selenium exhibit a synergistic effect in the male reproductive system, with the combined preparation demonstrating superior therapeutic effects compared to individual preparations. The purpose of this study was to explore the specific mechanism by which zinc and selenium mitigate reproductive toxicity induced by TG in male rats. Rats were randomly assigned to three groups: control group (C group), model group (M group, receiving TG at 30 mg/kg/day), and model + zinc + selenium group (ZS group). The ZS group was also given TG gavage for the first 4 weeks. Starting from the fifth week until the conclusion of the eighth week, the ZS group received an additional protective treatment of 10 mg/kg/day Zn and 0.1 mg/kg/day Se 4 h after TG administration. Following euthanasia, blood samples, rat testis, and epididymis tissues were collected for further experiments. Combined zinc-selenium treatment corrects the imbalance of zinc-selenium homeostasis in testicular tissue induced by TG. This is achieved by upregulating the expression of metal transcription factor (MTF1) and zinc transporters ZIP8 and ZIP14 and downregulating the expression of ZnT10. Improvement of zinc and selenium homeostasis enhanced the expression of zinc-containing enzymes (ADH, LDH, and ALP) and selenoproteins (GPx1 and SELENOP) in the testis. At the same time, zinc and selenium mitigate TG-induced reproductive damage by promoting the activity of antioxidant enzymes and upregulating the expression of proteins associated with the oxidative stress pathway, including Nrf2, Keap1, HO-1, PI3K, and p-AKT.
雷公藤多苷的长期使用可导致男性生殖损伤。研究表明，锌和硒在男性生殖系统中表现出协同作用，联合制剂的治疗效果优于单一制剂。本研究旨在探讨锌和硒缓解雷公藤多苷致雄性大鼠生殖毒性的具体机制。大鼠随机分为三组：对照组（C 组）、模型组（M 组，给予 30mg/kg/d 雷公藤多苷）和模型+锌+硒组（ZS 组）。ZS 组还在第 4 周进行了雷公藤多苷灌胃。从第 5 周开始到第 8 周结束，ZS 组在给予 TG 后 4 小时给予 10mg/kg/d 的锌和 0.1mg/kg/d 的硒进行额外的保护治疗。安乐死后，采集血样、大鼠睾丸和附睾组织进行进一步实验。联合锌硒治疗纠正了 TG 诱导的睾丸组织锌硒内稳态失衡。这是通过上调金属转录因子（MTF1）和锌转运体 ZIP8 和 ZIP14 的表达以及下调 ZnT10 的表达来实现的。锌和硒内稳态的改善增强了睾丸中含锌酶（ADH、LDH 和 ALP）和硒蛋白（GPx1 和 SELENOP）的表达。同时，锌和硒通过促进抗氧化酶的活性和上调与氧化应激途径相关的蛋白的表达来减轻 TG 诱导的生殖损伤，包括 Nrf2、Keap1、HO-1、PI3K 和 p-AKT。
