秦皮甲素减轻脂多糖刺激小鼠急性肾损伤和炎症反应的作用及其机制

doi:10.5246/jcps.2020.05.030

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (5): 322-332.DOI: 10.5246/jcps.2020.05.030

秦皮甲素减轻脂多糖刺激小鼠急性肾损伤和炎症反应的作用及其机制

程笑^1,2, 杨滢霖^1,2, 李伟瀚^1,2, 刘漫^1,2, 张姗姗^1,2, 王月华^1,2*, 杜冠华^1,2*

1. 中国医学科学院&北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室, 北京 100050
2. 中国医学科学院&北京协和医学院药物研究所药物靶点研究与新药筛选北京市重点实验室, 北京 100050

收稿日期:2019-10-26 修回日期:2019-12-04 出版日期:2020-05-31 发布日期:2020-03-12
基金资助:
The National Key Research & Development Plan (Grant No. 2018YFC0311005), the National Natural Science Foundation of China (Grant No. 81473383), the Significant New-Drugs Creation of Science and Technology Major Projects (Grant No. 2012ZX09103101-078), the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-3-007), and Innovation Fund for Doctoral Students of Beijing Union Medical College (Grant No. 2018-1007-04).

Esculin alleviates acute kidney injury and inflammation induced by LPS in mice and its possible mechanism

Xiao Cheng^1,2, Yinglin Yang^1,2, Weihan Li^1,2, Man Liu^1,2, Shanshan Zhang^1,2, Yuehua Wang^1,2*, Guanhua Du^1,2*

1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
2. Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2019-10-26 Revised:2019-12-04 Online:2020-05-31 Published:2020-03-12
Contact: Tel.: +86-10-63165313; +86-10-63165184, E-mail: wangyuehua@pku.org.cn; dugh@imm.ac.cn
Supported by:
The National Key Research & Development Plan (Grant No. 2018YFC0311005), the National Natural Science Foundation of China (Grant No. 81473383), the Significant New-Drugs Creation of Science and Technology Major Projects (Grant No. 2012ZX09103101-078), the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-3-007), and Innovation Fund for Doctoral Students of Beijing Union Medical College (Grant No. 2018-1007-04).

摘要/Abstract

摘要：

急性肾损伤是临床常见的严重疾病。秦皮甲素是一种香豆素类化合物, 前期研究发现秦皮甲素对糖尿病大鼠肾脏损伤具有保护作用, 本研究旨在探讨秦皮甲素对脂多糖(LPS)致小鼠急性肾损伤的作用及其可能机制。H&E染色观察肾脏形态; 测定血尿素氮(BUN)水平和血清肌酐含量评价肾功能; ELISA法检测炎症因子水平; RT-PCR和Western blotting分析炎症蛋白表达水平。结果表明, ES可减轻LPS所致的病理损伤和肾功能损伤, 降低血清BUN水平和肌酐含量; 此外, ES显著降低肾组织中IL-1β、IL-6和TNF-α、趋化因子MCP-1和细胞黏附分子ICAM-1等的释放。进一步研究发现,秦皮甲素在mRNA水平和蛋白水平下调LPS导致的小鼠肾组织中炎症通路蛋白P2X7、HMGB1、TLR4和MyD88的表达。以上结果表明, 秦皮甲素对LPS刺激所致急性肾损伤具有保护作用, 抑制炎症反应与下调P2X7和HMGB1/TLR4炎症通路相关。

关键词: 急性肾损伤, 秦皮甲素, 脂多糖, 炎症反应, 嘌呤能2X7受体, 高迁移率蛋白1

Abstract:

Acute kidney injury (AKI) is a common clinical serious illness. Esculin (ES) is a coumarin compound of traditional Chinese medicine Cortex Fraxini. Our previous study has found that ES protects against inflammation and renal damage in diabetic rats.In the present study, we aimed to investigate the effects and the possible mechanism of ES against lipopolysaccharides (LPS)-induced AKI in mice. Renal morphology was observed by H&E staining. Renal function was evaluated by blood urea nitrogen (BUN) level and creatinine content in serum. Inflammatory factor levels were measured by ELISA assay. The inflammatory proteins were analyzed by RT-PCR and Western blotting analysis. The results showed that ES alleviated LPS-induced pathological injury and renal dysfunction, and decreased BUN level and creatinine content in serum. In addition, ES significantly reduced the release of pro-inflammatory factors, including IL-1β, IL-6 and TNF-α, chemokine MCP-1 and cell adhesion molecule ICAM-1. Furthermore,the expressions of inflammatory pathway proteins P2X7, HMGB1, TLR4 and MyD88 both at the mRNA and protein levels were all down-regulated by ES in the kidney tissue of LPS-challenged mice. These results suggested ES protected against LPS-induced AKI through inhibiting P2X7 expression and HMGB1/TLR4 inflammatory pathway.

Key words: Acute kidney injury, Esculin, Lipopolysaccharide, Inflammation, Purinergic 2X7 receptor, High mobility group box 1

中图分类号:

R963

Supporting:

程笑, 杨滢霖, 李伟瀚, 刘漫, 张姗姗, 王月华, 杜冠华. 秦皮甲素减轻脂多糖刺激小鼠急性肾损伤和炎症反应的作用及其机制[J]. 中国药学(英文版), 2020, 29(5): 322-332.

Xiao Cheng, Yinglin Yang, Weihan Li, Man Liu, Shanshan Zhang, Yuehua Wang, Guanhua Du. Esculin alleviates acute kidney injury and inflammation induced by LPS in mice and its possible mechanism[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(5): 322-332.

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秦皮甲素减轻脂多糖刺激小鼠急性肾损伤和炎症反应的作用及其机制

Esculin alleviates acute kidney injury and inflammation induced by LPS in mice and its possible mechanism

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