目的 探讨右归丸对雷公藤多苷（TG）片所致Ⅱ型胶原诱导性关节炎（CIA）模型大鼠生殖毒性减毒作用及其机制。方法 采用牛Ⅱ型胶原乙酸溶液和弗氏完全佐剂诱导建立CIA大鼠模型，随机分为对照组、模型组、TG(72 mg·kg^-1)组及右归丸(3 g·kg^-1)+TG(72 mg·kg^-1)组，连续给药4周。实验期间对关节炎指数进行评分，实验结束时检测血清中雌二醇（E₂）、卵泡刺激素（FSH）和睾酮（T）含量，检测卵巢和睾丸脏器指数和组织病理学变化，通过转录组学进行RNA测序与差异基因筛选，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析；采用Western blotting法进行关键靶点验证。结果 与对照组比较，模型组大鼠关节炎指数显著升高（P<0.01）；与模型组比较，TG组和右归丸+TG组显著降低（P<0.05、0.01）。与模型组比较，TG组的E₂和T含量显著降低（P<0.05）；与TG组比较，右归丸+TG组的E₂和T含量显著回升（P<0.01）。与模型组比较，TG组卵巢和睾丸组织损伤明显，表现为卵泡数量减少、颗粒层变薄、精子数量减少等；与TG组比较，右归丸+TG组的组织病理损伤显著缓解。卵巢样本GO富集分析集中在“女性生殖发育”相关过程，如ovulation cycle process（排卵周期过程）、ovulation cycle（排卵周期）、female gonad development（女性性腺发育）、mammalian oogenesis stage（哺乳动物卵子发生阶段）；KEGG富集分析集中在过氧化物酶体增殖物激活受体（PPAR）、脂肪酸代谢和转化生长因子-β（TGF-β）信号通路。睾丸样本GO富集分析集中在“脂肪细胞发育与免疫应答”过程，如white fat cell differentiation（白色脂肪细胞分化）、fat cell differentiation（脂肪细胞分化）；KEGG富集分析集中在过氧化物酶体增殖物激活受体-γ（PPAR）、脂肪细胞脂解的调控通路。与模型组比较，TG组大鼠骨形态发生蛋白2（BMP2）、抗缪勒氏管激素（AMH）、抑制素A（INHBA）、抑制素B（INHBB）和脂肪酸结合蛋白4（FABP4）蛋白表达水平明显降低（P<0.05、0.01）；与TG组比较，右归丸+TG组上述蛋白表达水平显著升高（P<0.05、0.01）。结论 右归丸能够显著减轻雷公藤多苷对CIA模型大鼠的生殖毒性，与其能调节TGF-β和PPAR信号通路密切相关。

Objective To explore the attenuating effect of Yougui Pills on reproductive toxicity in II collagen-induced arthritis（CIA） model rats induced by Tripterygium Glycosides（TG） Tablets and its underlying mechanism. Methods A CIA rat model was established by using type II collagen acetate solution and complete Freund’s adjuvant. The rats were randomly divided into the control group, the model group, the TG(72 mg·kg^-1) group and the Yougui Pills(3 g·kg^-1) + TG(72 mg·kg^-1) group, and were continuously administered for 4 weeks. During the experiment, the degree of joint redness and swelling was scored. At the end of the experiment, the contents of estradiol（E₂）, follicle-stimulating hormone（FSH） and testosterone（T） in the serum were detected. The organ index and histopathological changes of the ovaries and testes were also examined. RNA sequencing and differential gene screening were performed through transcriptomics, and gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were conducted. Western blotting was used to verify the key targets. Results Compared with the control group, the arthritis index of the model group was significantly increased（P ＜0.01）. Compared with the model group, the arthritis index of the TG group and the Yougui Pills + TG group was significantly decreased（P ＜0.05, 0.01）. Compared with the model group, the contents of E₂ and T in the TG group were significantly decreased（P ＜0.05）. Compared with the TG group, the contents of E₂ and T in the Yougui Pills + TG group were significantly increased（P ＜0.01）. Compared with the model group, the TG group showed obvious damage to the ovaries and testes, manifested as a decrease in the number of follicles, thinning of the granulosa layer, and a decrease in the number of sperm. Compared with the TG group, the histopathological damage of the Yougui Pills + TG group was significantly alleviated. The GO enrichment analysis of the ovarian samples was concentrated on the processes related to "female reproductive development", such as ovulation cycle process, ovulation cycle, female gonad development, and mammalian oogenesis stage. The KEGG enrichment analysis was concentrated on the peroxisome proliferator-activated receptor（PPAR）, fatty acid metabolism, and transforming growth factor-β（TGF-β） signaling pathways. The GO enrichment analysis of the testicular samples was concentrated on the processes of "adipocyte development and immune response", such as white fat cell differentiation and fat cell differentiation. The KEGG enrichment analysis was concentrated on the peroxisome proliferator-activated receptor-γ（PPAR） and the regulation of adipocyte lipolysis pathways. Compared with the model group, the protein expression levels of bone morphogenetic protein 2（BMP2）, anti-Müllerian hormone（AMH）, inhibin A（INHBA）, inhibin B（INHBB）, and fatty acid binding protein 4（FABP4） in the TG group were significantly decreased（P ＜0.05, 0.01）. Compared with the TG group, the protein expression levels of the above proteins in the Dui Gui Wan + TG group were significantly increased（P ＜0.05, 0.01）. Conclusion Yougui Pills can significantly alleviate the reproductive toxicity of TG in CIA model rats, which is closely associated with its regulatory effect on the TGF-β and PPAR signaling pathways.

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山西省基础研究计划项目(20210302123235); 山西中医药大学研究生科研实践创新项目(X2025KY022)