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目的:研究金匮肾气丸对无精子症模型小鼠生精能力恢复作用的睾丸全基因表达谱。方法:12周龄NIH雄性小鼠按照40 mg·kg-1单次ip 2%白消安药液制备无精子症小鼠动物模型,观察42 d后,给予金匮肾气丸中药1 g·kg-1,ig给药78 d(2个生精周期),以造模后模型组(自然恢复)、溶媒和正常动物为3种对照,通过基因芯片技术检测服用金匮肾气丸的无精子小鼠与正常对照小鼠之间睾丸中差异表达的基因,对这些基因按照表达差异程度、功能注释和Pathway进行分析。结果:动物实验结果显示:无精子症模型小鼠经过78 d的金匮肾气丸ig给药后,在动物体质量、生殖器官组织质量和指数、附睾精子质量(活动率、活动力、浓度)等与生殖能力相关的指标上与模型组比较有明显的改善。基因表达谱芯片结果显示:服用金匮肾气丸的无精子小鼠与正常组相比,睾丸中差异表达2倍以上的基因804个(占2.53%),其中上调517个,低于正常表达1/2的287个,差异表达4倍以上的基因134个(占0.42%)其中上调127个,低于正常表达1/4的7个,提示以正向促进/上调作用为主,以负向抑制/下调作用为辅;主要通过对细胞周期、细胞因子-细胞因子受体作用、Ecm受体作用、Jak-Stat信号通路、Mapk信号通路、Notch信号通路、Toll样受体信号通路和Wnt信号通路等8个信号通路系统的调节实现生精能力的提高。结论:金匮肾气丸有助于促进无精子小鼠生精能力的恢复。通过基因芯片检测后与正常小鼠相比,这种促进作用可能是通过多途径对生精干细胞中与细胞增殖分裂相关基因的正向调节实现的。
OBJECTIVE: To study the testicular gene expression profile of Jingui Shenqi Pill in restoring the spermatogenic capacity of azoospermia model mice. Methods: Azoospermic mouse model was established in 12-week-old NIH male mice according to a single ip 2% busulfan 40 mg · kg-1. After 42 days, kg-1, ig administration for 78 days (2 spermatogenic cycles). The model group (natural recovery), vehicle and normal animal were used as control. The genes differentially expressed in the testes between sperm mice and normal control mice were analyzed for differences in gene expression, functional annotations, and Pathway. Results: The results of animal experiments showed that after the ig administration of Jinguishenqi Pill for 78 days in azoospermia model mice, the body weight, genital tissue quality and index, epididymal sperm quality (activity rate, activity, concentration ) And other indicators of reproductive capacity and the model group compared to significant improvement. Gene expression microarray results showed that compared with normal group, azoospermic mice taking Jinguishenqi Pill showed 804 genes (2.53%) which were more than twice as many as those in normal testes, of which 517 were up-regulated, which was lower than the normal expression 1/2 of the 287 genes, more than 4 times more than differentially expressed 134 genes (0.42%), of which 127 were up, compared with the normal expression of 1/4 of 7, suggesting that the positive promotion / up-acting mainly to negative Which is complementary to inhibition / down-regulation; mainly through the inhibition of cell cycle, cytokine-cytokine receptor, Ecm receptor, Jak-Stat signaling pathway, Mapk signaling pathway, Notch signaling pathway, Toll-like receptor signaling pathway and Wnt Signal path and other 8 signal path adjustment system to achieve sperm ability to improve. Conclusion: Jinkuishenqiwan can promote the recovery of spermatogenesis in azoospermic mice. Compared with normal mice, this promotion effect may be achieved through multiple pathways on the positive regulation of cell proliferation and division-related genes in spermatogenic stem cells.