Zhang Bo, Su Hang, Ren Xian-Qing, Li Wei-Xia, Ding Ying, Zhang Xia, Zhai Wen-Sheng, Song Chun-Dong
the First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000,China.
Zhongguo Zhong Yao Za Zhi. 2019 Aug;44(16):3478-3485. doi: 10.19540/j.cnki.cjcmm.20190527.402.
Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.
雷公藤多苷片具有良好的抗炎和免疫调节活性，但其对生殖系统的损害较为显著。该研究组之前的研究发现，菟丝子黄酮可通过调节生精细胞周期、凋亡及相关蛋白表达来改善雷公藤多苷片所致的生精细胞损伤，但其在基因水平的作用机制仍不明确。本研究应用Illumina高通量测序平台对菟丝子黄酮和雷公藤多苷片干预后的大鼠生精细胞进行转录测序。筛选出差异表达基因，并对差异表达基因进行GO富集和KEGG通路分析，以探讨菟丝子黄酮改善雷公藤多苷片所致生殖损伤的机制。结果显示，与空白组相比，雷公藤多苷片组筛选出794个上调基因和491个下调基因。与雷公藤多苷片组相比，菟丝子黄酮+雷公藤多苷片组筛选出440个上调基因和784个下调基因。其中，与生殖功能密切相关的基因是DNMT3 L。GO功能和KEGG信号通路富集分析表明，上述差异表达基因主要富集在细胞、细胞过程、催化活性、结合、卵巢类固醇合成、甲状腺激素等功能和通路。甲状腺激素信号通路是两个对照组共同的富集通路。总之，菟丝子黄酮对雷公藤多苷片所致男性生殖损伤具有良好的治疗效果。其机制可能与上调DNMT3 L基因及干预甲状腺激素信号通路密切相关。同时，众多差异基因的发现为研究菟丝子黄酮与雷公藤多苷片配伍减毒增效的机制提供了有价值的信息。
