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甘草酸通过调节HMGB1/TLR4通路改善小鼠放射性肠炎。

Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway.

作者信息

Zhang Xiao-Min, Hu Xiao, Ou Jin-Ying, Chen Shan-Shan, Nie Ling-Hui, Gao Lei, Zhu Ling-Ling

机构信息

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

Traditional Chinese Pharmacological Laboratory, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

出版信息

Evid Based Complement Alternat Med. 2020 May 31;2020:8653783. doi: 10.1155/2020/8653783. eCollection 2020.

DOI:10.1155/2020/8653783
PMID:32595744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7281845/
Abstract

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF- in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-, IL-6, IL-1, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-, IL-6, IL-1, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

摘要

放射性肠炎是腹部和盆腔恶性肿瘤放疗的常见副作用,可导致患者放疗耐受性及生活质量下降。已证实甘草酸(GL)具有显著的抗炎活性。然而,其在放射性肠炎中的抗炎作用鲜为人知。在本研究中,我们旨在探讨GL对放射性肠炎的潜在抗炎作用,并阐明可能涉及的潜在分子机制。将C57BL/6小鼠进行6.5 Gy腹部X线照射以建立放射性肠炎模型。进行苏木精-伊红染色以分析空肠的病理变化。通过免疫化学分析空肠中TNF-的表达。采用酶联免疫吸附测定法测定血清中TNF-、IL-6、IL-1和HMGB1等炎性细胞因子水平。使用D-木糖吸收试验检测肠道吸收能力。通过蛋白质免疫印迹法和免疫荧光染色分析HMGB1和TLR4水平。我们发现GL显著减轻肠道损伤,降低TNF-、IL-6、IL-1和HMGB1等炎性细胞因子水平。此外,GL处理显著下调HMGB1/TLR4信号通路。总之,这些发现表明GL通过抑制肠道损伤、炎症反应以及HMGB1/TLR4信号通路对放射性肠炎具有保护作用。因此,GL可能是治疗放射性肠炎的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/ee03bcedc9b1/ECAM2020-8653783.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/539d310f8c80/ECAM2020-8653783.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/9c6a36883ac4/ECAM2020-8653783.002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/b2209e871d95/ECAM2020-8653783.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/ee03bcedc9b1/ECAM2020-8653783.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/539d310f8c80/ECAM2020-8653783.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/9c6a36883ac4/ECAM2020-8653783.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/fed3ed2f4e0f/ECAM2020-8653783.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/b2209e871d95/ECAM2020-8653783.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/7281845/ee03bcedc9b1/ECAM2020-8653783.005.jpg

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