背景:凉血固原益肾汤的疗效,中药,在高剂量辐射暴露后,已在治疗辐射引起的肠损伤(RIII)和保持肠完整性和功能方面得到了科学证明。然而,需要进一步的研究来全面阐明LGYD治疗效果的确切机制,从而为辐射防护提供潜在的药物选择.
目的:本研究旨在阐明LGYD通过调节肠道菌群(GM)对RIII发挥治疗作用的潜在机制。
方法:采用16srRNA分析来评估不同剂量的全身照射(WBI)对GM的影响,以建立适合本研究的模型。使用16srRNA和SCFA定量评价LGYD对GM和SCFA的作用。利用UHPLC-QE-MS鉴定LGYD以及含LGYD药物的血清(LGYD-DS)中的活性组分。随后,免疫荧光和免疫组织化学染色用于验证LGYD和/或特征性微生物群对体内RIII恢复的影响.LGYD-DS的影响,特征植物区系,通过测量肠道类器官模型中的类器官表面积来评估肠干细胞(ISC)和SCFA。
结果:剂量为8.5Gy的全身照射对GM的物种组成和丰度有显著影响,用作体内模型。LGYD显著提高存活率并促进从RIII的恢复。此外,LGYD表现出显着增加的Akkermansiamuciniphia(AKK)的丰度和SCFA的水平,特别是异丁酸。LGYD-DS由来自LGYD草药的七个主要成分组成。体内实验表明,LGYD和AKK均大大提高了辐射后的存活率,并促进了肠结构和功能的恢复过程。在类器官模型中,用LGYD-DS治疗,AKK上清液或异丁酸显著增加类器官表面积。
结论:LGYD有可能通过促进肠干细胞的恢复来增强RIII,这与AKK丰度的上调和SCFA的产生密切相关,特别是异丁酸。
BACKGROUND: 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.
OBJECTIVE: This study aims to elucidate the potential mechanism through which LGYD exerts its therapeutic effects on RIII by modulating the gut microbiota (GM).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.