研究动态
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凉血固元益肾汤对胃肠急性辐射综合症大鼠肠道干细胞和紧密连接蛋白的治疗机制。

Therapeutic mechanism of Liangxue-Guyuan-Yishen decoction on intestinal stem cells and tight junction proteins in gastrointestinal acute radiation syndrome rats.

发表日期:2023 Sep 11
作者: Ziqiao Yan, Bofeng Yin, Yuguo Wang, Zhexin Ni, Jian Feng, Qianyu Yang, Xiao Li, Heng Zhu, Yongqi Dou
来源: Experimental Hematology & Oncology

摘要:

基于先前的研究,采用传统中医理论改进了胃肠急性放射综合征(GI-ARS)的药物组合。本研究的目的是研究梁血骨髓益肾汤(LGYD)对GI-ARS的治疗机制,并为放射损伤的治疗提供新方案。在此,我们调查了LGYD对GI-ARS大鼠模型中的肠道干细胞(ISCs)的影响。分析大鼠的健康状况、存活率以及LGYD对肠道的保护效果。利用液相色谱-质谱联用技术(LC-MS)检测LGYD中的活性成分。利用免疫组化、免疫印迹(WB)和逆转录定量聚合酶链反应(RT-qPCR)探索ISC增殖、肠道上皮紧密连接蛋白(TJ)的表达以及相关调节途径。采用网络药理学分析筛选肠道恢复中WNT和MEK/ERK途径的作用,并通过WB和RT-qPCR进行验证。LGYD的给药显著改善了GI-ARS大鼠的健康状况和存活率。病理分析显示,LGYD改善了放射引起的肠道损伤,显著促进了肠道小窝中LGR5+干细胞的再生,上调了TJ蛋白,并加速了辐射大鼠的小窝重建。LC-MS检测到≥13种成分可能有助于LGYD的保护效应。综上所述,LGYD可促进辐射损伤后小窝细胞的增殖和ISC的增多,这种效应可能与WNT和MEK/ERK途径有关。© 2023作者。由牛津大学出版社代表日本放射研究学会和日本放射肿瘤学会发表。
On the basis of the previous research, the Traditional Chinese Medicine theory was used to improve the drug composition for gastrointestinal acute radiation syndrome (GI-ARS). The purpose of this study was to study the therapeutic mechanism of Liangxue-Guyuan-Yishen decoction (LGYD) on GI-ARS and to provide a new scheme for the treatment of radiation injury. Here, we investigated the effects of LGYD on intestinal stem cells (ISCs) in a GI-ARS rat model. Rat health and survival and the protective efficacy of LGYD on the intestines were analyzed. The active principles in LGYD were detected using liquid chromatography-mass spectrometry (LC-MS). ISC proliferation, intestinal epithelial tight junction (TJ) protein expression and regulatory pathways were explored using immunohistochemistry, western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Involvement of the WNT and MEK/ERK pathways in intestinal recovery was screened using network pharmacology analysis and validated by WB and RT-qPCR. LGYD administration significantly improved health and survival in GI-ARS rats. Pathological analysis showed that LGYD ameliorated radiation-induced intestinal injury and significantly promoted LGR5+ stem cell regeneration in the intestinal crypts, upregulated TJ protein, and accelerated crypt reconstruction in the irradiated rats. LC-MS revealed ≥13 constituents that might contribute to LGYD's protective effects. Collectively, LGYD can promote crypt cell proliferation and ISCs after radiation damage, the above effect may be related to WNT and MEK/ERK pathway.© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.