Department of Traditional Chinese Medicine, the Sixth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China; Chinese PLA Medical School, Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, PR China.
Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Medical University, Shanghai, PR China.
Phytomedicine. 2024 Sep;132:155888. doi: 10.1016/j.phymed.2024.155888. Epub 2024 Jul 20.
The efficacy of Liangxue Guyuan Yishen Decoction (LGYD), a traditional Chinese medicine, has been scientifically proven in the treatment of radiation-induced intestinal injury (RIII) and preservation of intestinal integrity and function following high-dose radiation exposure. However, further investigation is required to comprehensively elucidate the precise mechanisms underlying the therapeutic effects of LGYD in order to provide potential pharmaceutical options for radiation protection.
This study aims to elucidate the potential mechanism through which LGYD exerts its therapeutic effects on RIII by modulating the gut microbiota (GM).
16 s rRNA analysis was employed to assess the impact of varying doses of whole body irradiation (WBI) on GM in order to establish an appropriate model for this study. The effects of LGYD on GM and SCFA were evaluated using 16 s rRNA and Quantification of SCFA. UHPLC-QE-MS was utilized to identify the active components in LGYD as well as LGYD drug containing serum (LGYD-DS). Subsequently, immunofluorescence and immunohistochemical staining were conducted to validate the influence of LGYD and/or characteristic microbiota on RIII recovery in vivo. The effects of LGYD-DS, characteristic flora, and SCFA on intestinal stem cell (ISC) were assessed by measuring organoid surface area in intestinal organoid model.
The species composition and abundance of GM were significantly influenced by whole-body irradiation with a dose of 8.5 Gy, which was used as in vivo model. LGYD significantly improves the survival rate and promotes recovery from RIII. Additionally, LGYD exhibited a notable increase in the abundance of Akkermansia muciniphila (AKK) and levels of SCFA, particularly isobutyric acid. LGYD-DS consisted of seven main components derived from herbs of LGYD. In vivo experiments indicated that both LGYD and AKK substantially enhanced the survival rate after radiation and facilitated the recovery process for intestinal structure and function. In the organoid model, treatment with LGYD-DS, AKK supernatant or isobutyric acid significantly increased organoid surface area.
LGYD has the potential to enhance RIII by promoting the restoration of intestinal stem cell, which is closely associated with the upregulation of AKK abundance and production of SCFA, particularly isobutyric acid.
梁雪归脾益肾汤（LGYD）是一种中药，其在治疗放射性肠损伤（RIII）和高剂量辐射暴露后保持肠道完整性和功能方面的疗效已得到科学证实。然而，为了为辐射防护提供潜在的药物选择，需要进一步研究以全面阐明 LGYD 治疗效果的精确机制。
本研究旨在通过调节肠道微生物群（GM）来阐明 LGYD 对 RIII 发挥治疗作用的潜在机制。
采用 16s rRNA 分析评估不同剂量全身照射（WBI）对 GM 的影响，以建立本研究的合适模型。采用 16s rRNA 和 SCFA 定量评估 LGYD 对 GM 和 SCFA 的影响。采用 UHPLC-QE-MS 鉴定 LGYD 中的活性成分以及 LGYD 含药血清（LGYD-DS）。随后，通过免疫荧光和免疫组织化学染色验证 LGYD 和/或特征菌群对体内 RIII 恢复的影响。通过测量肠道类器官模型中的类器官表面积来评估 LGYD-DS、特征菌群和 SCFA 对肠干细胞（ISC）的影响。
全身照射 8.5Gy 作为体内模型，显著影响 GM 的物种组成和丰度。LGYD 显著提高了存活率并促进了 RIII 的恢复。此外，LGYD 显著增加了 Akkermansia muciniphila（AKK）的丰度和 SCFA 的水平，特别是异丁酸。LGYD-DS 由 LGYD 草药中的七种主要成分组成。体内实验表明，LGYD 和 AKK 均可显著提高辐射后的存活率，并促进肠道结构和功能的恢复。在类器官模型中，LGYD-DS、AKK 上清液或异丁酸处理均显著增加了类器官表面积。
LGYD 具有通过促进肠干细胞恢复来增强 RIII 的潜力，这与 AKK 丰度的上调和 SCFA 的产生密切相关，特别是异丁酸。
