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基于Nrf2介导的睾丸抗氧化防御探究女贞子及其酒制品对雷公藤多苷致生殖毒性的减毒机制

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中草药 | 药理与临床 2026,57(7): 2614-2621

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中草药 |药理与临床 2026 , 57 (7) : 2614 -2621

基于Nrf2介导的睾丸抗氧化防御探究女贞子及其酒制品对雷公藤多苷致生殖毒性的减毒机制

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王倩¹, 王君明^1,2,3,4, 张月月^1,2, 巫晓慧^1,2, 王彦嵋^1,2, 弓明珠^1,2, 何庆文^1,2, 秦玲玉¹, 杜晨杰¹, 李琬莹¹

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通讯作者:

王君明

作者简介:

王倩: 王倩(2001-),女,硕士研究生,主要从事中药功效机制与安全性评价研究。E-mail:qianwang0223@163.com

Mechanism of Ligustri Lucidi Fructus with its wine-processed product on attenuating Tripterygium wilfordii polycoride-induced reproductive toxicity based on Nrf2-mediated testicular antioxidant defense

WANG Qian, WANG Junming, ZHANG Yueyue, WU Xiaohui, WANG Yanmei, GONG Mingzhu, HE Qingwen, QIN Lingyu, DU Chenjie, LI Wanying

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doi: 10.7501/j.issn.0253-2670.2026.07.016

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目的探究女贞子Ligustri Lucidi Fructus及其酒制品对雷公藤多苷致生殖毒性的减毒作用差异，并基于核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）介导的睾丸抗氧化防御探究其减毒机制。方法 ICR小鼠连续28 d ig雷公藤多苷（40 mg/kg），同时ig女贞子或其酒制品进行干预。采用试剂盒检测血清中睾酮和睾丸组织中氧化应激相关指标的水平；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察睾丸组织病理变化；采用Western blotting和qRT-PCR检测睾丸组织Nrf2、血红素加氧酶-1（heme oxygenase-1，HO-1）、还原型烟酰胺腺嘌呤二核苷酸磷酸醌脱氢酶1（nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1，NQO1）蛋白及mRNA表达。结果雷公藤多苷致小鼠睾丸生精小管结构松散，生精细胞层次减少，成熟精子数量显著减少，睾酮水平显著降低（P＜0.01），睾丸脂质过氧化产物丙二醛（malondialdehyde，MDA）水平显著升高（P＜0.01）；女贞子（1、2 g/kg）能够显著抑制上述指标异常（P＜0.05、0.01），且女贞子（2 g/kg）还能够显著提升抗氧化酶活性（P＜0.05、0.01）；女贞子酒制品（1、2 g/kg）均能够显著抑制上述指标异常（P＜0.01），且女贞子酒制品（2 g/kg）能够更全面地逆转氧化应激失衡（P＜0.01），相同剂量下女贞子酒制品的减毒效果明显优于其生品（P＜0.05、0.01）。机制分析发现，雷公藤多苷显著下调小鼠睾丸组织Nrf2及其下游分子HO-1、NQO1的表达（P＜0.01），而女贞子及其酒制品（1、2 g/kg）能够显著上调Nrf2及其下游分子HO-1、NQO1的表达（P＜0.05、0.01），其中女贞子酒制品的作用显著优于女贞子（P＜0.01）。结论女贞子及其酒制品均能够减轻雷公藤多苷引起的睾丸生殖毒性，且酒制品的减毒效果显著优于生品，其机制可能与增强Nrf2介导的睾丸抗氧化防御相关。

关键词

女贞子 / 酒制 / 生殖毒性 / Nrf2 / 氧化应激 / 特女贞苷 / 红景天苷

Abstract

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Objective To explore the differential attenuation effects of Nüzhenzi (Ligustri Lucidi Fructus) and its wine-processed product on Tripterygium wilfordii polycoride (TWP)-induced reproductive toxicity, and to investigate its attenuation mechanism based on nuclear factor erythroid 2-related factor 2 (Nrf2) mediated testicular antioxidant defense. Methods ICR mice were ig TWP (40 mg/kg) for 28 d, and intervention was also given with Ligustri Lucidi Fructus or its wine-processed products. Reagent kits were used to detect the levels of testosterone in serum and oxidative stress-related indicators in testicular tissue. Hematoxylin-eosin (HE) staining was used to observe pathological changes in testicular tissue. Western blotting and qRT-PCR were used to detect the protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1) in testicular tissue. Results TWP caused a loose structure of seminiferous tubules in testes of mice, a decrease in level of spermatogenic cells, a significant reduction in number of mature sperm, a significant decrease in testosterone levels (P < 0.01), and a significant increase in the level of malondialdehyde (MDA), a lipid peroxidation product in testes (P < 0.01). Ligustri Lucidi Fructus (1, 2 g/kg) could significantly inhibit the abnormal indicators mentioned above (P < 0.05, 0.01), and Ligustri Lucidi Fructus (2 g/kg) could also significantly enhance the activity of antioxidant enzymes (P < 0.05, 0.01). Ligustri Lucidi Fructus wine-processed products (1, 2 g/kg) could significantly inhibit the abnormal indicators mentioned above (P < 0.01), and Ligustri Lucidi Fructus wine-processed products (2 g/kg) could more comprehensively reverse oxidative stress imbalance (P < 0.01). At the same dose, the detoxification effect of Ligustri Lucidi Fructus wine-processed products was significantly better than that of their raw products (P < 0.05, 0.01). Mechanism analysis revealed that TWP significantly down-regulated the expressions of Nrf2 and its downstream molecules HO-1 and NQO1 in testicular tissue of mice (P < 0.01), while Ligustri Lucidi Fructus and its wine-processed products (1, 2 g/kg) significantly up-regulated the expressions of Nrf2 and its downstream molecules HO-1 and NQO1 (P < 0.05, 0.01), with Ligustri Lucidi Fructus wine-processed products showing a significantly better effect than Ligustri Lucidi Fructus (P < 0.01). Conclusion Ligustri Lucidi Fructus and its wine-processed products could alleviate the testicular reproductive toxicity caused by TWP, and the detoxification effect of wine-processed products is significantly better than that of raw products. The mechanism may be related to enhancing Nrf2 mediated testicular antioxidant defense.

Key words

Ligustri Lucidi Fructus / wine processing / reproductive toxicity / Nrf2 / oxidative stress / specneuzhenide / salidroside

引用本文

王倩, 王君明, 张月月, 巫晓慧, 王彦嵋, 弓明珠, 何庆文, 秦玲玉, 杜晨杰, 李琬莹. 基于Nrf2介导的睾丸抗氧化防御探究女贞子及其酒制品对雷公藤多苷致生殖毒性的减毒机制. 中草药, 2026 , 57 (7) : 2614 -2621 . DOI: 10.7501/j.issn.0253-2670.2026.07.016

WANG Qian, WANG Junming, ZHANG Yueyue, WU Xiaohui, WANG Yanmei, GONG Mingzhu, HE Qingwen, QIN Lingyu, DU Chenjie, LI Wanying. Mechanism of Ligustri Lucidi Fructus with its wine-processed product on attenuating Tripterygium wilfordii polycoride-induced reproductive toxicity based on Nrf2-mediated testicular antioxidant defense[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (7) : 2614 -2621 . DOI: 10.7501/j.issn.0253-2670.2026.07.016

基金

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中原科技创新领军人才项目 (254200510005); 河南省高校科技创新团队支持计划项目 (26IRTSTHN020); 河南省自然科学基金青年科学基金项目 (252300423825); 河南中医药大学2024年度研究生科研创新类项目 (2024KYCX035)

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2026年第57卷第7期

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doi: 10.7501/j.issn.0253-2670.2026.07.016

接收时间：2025-11-12
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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