研究动态
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综合转录组和代谢组学分析揭示了改良当归补血汤对辐射诱导性白细胞减少症的保护机制。

Integrated transcriptomic and metabolomic profiles reveal the protective mechanism of modified Danggui Buxue decoction on radiation-induced leukopenia in mice.

发表日期:2023
作者: Wei Chen, Jiayun Xin, Xintong Wei, Qianqian Ding, Yunheng Shen, Xike Xu, Yanping Wei, Yanhui Lv, Jie Wang, Zhanhong Li, Weidong Zhang, Xianpeng Zu
来源: Frontiers in Pharmacology

摘要:

放射線引起的白血球減少會阻礙對癌症的持續治療。党参补血汤(DBD)因其低毒性和明确的治疗效果而在临床上广泛应用,能够增加白细胞数量。同时,已经证明淫羊藿苷(ICT)也可以促进外周血细胞增殖。然而,目前还没有研究证实由DBD和ICT组成的改良党参补血汤(MDBD)对放射病引发的白细胞减少的疗效。在本研究中,我们采用3.5Gy的全身照射模型诱导小鼠白细胞减少。药效学研究结果显示MDBD通过改善骨髓核细胞的活性,减轻骨髓损伤,调节脾指数和调节造血因子,能够显著增加外周血白细胞数量以缓解白细胞减少。我们还分析了代谢组学和转录组学的综合结果,并发现MDBD通过靶向类固醇生物合成和IL-17信号通路来缓解白细胞减少和减轻骨髓损伤,其中关键基因是Jun,Cxcl2和Egr1。因此,我们的研究为中药方剂与小分子药物的组合治疗提供了有效性和兼容性的依据。版权所有 © 2023 Chen, Xin, Wei, Ding, Shen, Xu, Wei, Lv , Wang, Li, Zhang 和 Zu。
Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.Copyright © 2023 Chen, Xin, Wei, Ding, Shen, Xu, Wei, Lv, Wang, Li, Zhang and Zu.