目的 探讨淫羊藿苷对聚苯乙烯纳米塑料诱导的睾丸组织结构与功能损伤的保护作用及其可能机制。方法 通过ig聚苯乙烯纳米塑料悬液5 mg/kg，连续28 d，建立生殖损伤模型。将50只6周龄的雄性BALB/c小鼠随机分为对照组、模型组及淫羊藿苷低、中、高剂量（25、50、100 mg/kg）组，每组10只，ig治疗21 d。收集眼眶血及睾丸，计算睾丸脏器指数；HE染色观察睾丸组织结构；ELISA法检测血清睾酮水平；比色法检测睾丸组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）活力及丙二醛（MDA）的水平；Western blotting检测B细胞淋巴瘤2（Bcl-2）、半胱天冬蛋白酶-3（Caspase-3）、cleaved Caspase-3以及核因子E2相关因子2（Nrf2）、血红素氧合酶1（HO-1）蛋白表达水平。结果 与对照组相比，模型组小鼠生精上皮结构紊乱，生精细胞数量减少，血清睾酮水平显著降低（P＜0.001），睾丸组织SOD、GPx活力下降（P＜0.001），MDA水平升高（P＜0.001），Bcl-2蛋白表达下调（P＜0.001），cleaved Caspase-3蛋白表达上调（P＜0.001），Nrf2及HO-1蛋白表达下调（P＜0.05）。淫羊藿苷干预后，生精上皮结构得到改善，生精细胞数量增加，血清睾酮水平回升（P＜0.05、0.001），淫羊藿苷100 mg/kg组可显著提升SOD、GPx活力并降低MDA水平（P＜0.001），上调Bcl-2、Nrf2及HO-1蛋白表达（P＜0.001），下调cleaved Caspase-3蛋白表达（P＜0.001）。结论 淫羊藿苷可有效改善聚苯乙烯纳米塑料所致的小鼠睾丸损伤，其机制可能与激活Nrf2/HO-1信号通路、增强抗氧化能力、抑制生精细胞凋亡有关。

Objective investigate the protective effect of icariin on testicular structural and functional damage induced by polystyrene nanoplastics and to elucidate its potential molecular mechanism. Methods A reproductive injury mouse model was established by intragastric administration of polystyrene nanoplastics suspension at 5 mg/kg for 28 consecutive days. Fifty 6-week-old male BALB/c mice were randomly divided into control group, model group, and low-, medium- and high-dose icariin groups (25, 50, 100 mg/kg), with 10 mice in each group. Mice in each group received intragastric intervention for 21 d. Orbital blood and testicular tissues were collected, and testicular organ index was calculated. Testicular histological changes were observed by HE staining. Serum testosterone level was measured by ELISA. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in testicular tissues were determined by colorimetric assay. Western blotting was performed to detect the protein levels of B-cell lymphoma-2 (Bcl-2), caspase-3, cleaved-caspase-3, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Results Compared with the control group, the model group exhibited disorganized seminiferous epithelium, reduced number of spermatogenic cells, significantly decreased serum testosterone (P < 0.001), declined SOD and GPx activities (P< 0.001), elevated MDA content (P < 0.001), down-regulated Bcl-2 protein expression (P < 0.001), up-regulated cleaved-caspase-3 protein expression (P< 0.001), as well as decreased Nrf2 and HO-1 protein levels (P < 0.05). After icariin intervention, the structure of seminiferous epithelium was restored and the number of spermatogenic cells increased, accompanied by recovered serum testosterone levels (P < 0.05, 0.001). The 100 mg/kg icariin group markedly increased SOD and GPx activities, reduced MDA level (P < 0.001), up-regulated Bcl-2, Nrf2 and HO-1 protein expression (P < 0.001), and down-regulated cleaved-caspase-3 protein expression (P < 0.001). Conclusion Icariin can effectively alleviate testicular injuries induced by polystyrene nanoplastics in mice. The underlying mechanism may be related to the activation of Nrf2/HO-1 signaling pathway, enhancement of antioxidant capacity and inhibition of spermatogenic cell apoptosis.

R285.5

国家自然科学基金资助项目（82460290）；毕节市科技厅项目（毕科联合84号）