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香橙素通过抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路的磷酸化来减轻脂多糖(LPS)诱导的肾脏细胞凋亡和炎症。

Aromadendrin alleviates LPS-induced kidney apoptosis and inflammation by inhibiting phosphorylation of MAPK and NF-κB signaling pathways.

作者信息

Ma Xiaohong, Liu Wenhua, Wang Bin, Shi Feizhuang

机构信息

Department of Nephrology, Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen, China.

Department of Internal Medicine, Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen, China.

出版信息

Histol Histopathol. 2025 Feb;40(2):249-258. doi: 10.14670/HH-18-770. Epub 2024 May 30.

DOI:10.14670/HH-18-770
PMID:38873767
Abstract

BACKGROUND

Excessive inflammation and apoptosis in kidneys are critical players in the pathogenesis of acute kidney injury (AKI). Aromadendrin is a natural flavonoid characterized by anti-inflammatory, anti-apoptotic, and antioxidant actions. Thus, we investigated the roles and mechanisms of aromadendrin in the development of AKI.

METHODS

Lipopolysaccharide (LPS) was used to induce AKI mice, and one hour after LPS challenge, the mice received oral administration of aromadendrin or vehicle. Renal functions were assessed by measuring blood urea nitrogen and creatinine in serum. Histological changes were determined by hematoxylin and eosin staining. Apoptotic cells of renal tissues were detected by TUNEL staining. Gene expression was measured by western blotting and RT-qPCR.

RESULTS

Aromadendrin alleviated LPS-induced renal dysfunctions and histological defects in mice. Additionally, aromadendrin suppressed excessive inflammation and tissue apoptosis in the kidneys of LPS-induced AKI mice. Mechanistically, aromadendrin blocked the activation of NF-κB and MAPK pathways in LPS-induced AKI mice.

CONCLUSION

Aromadendrin alleviates LPS-stimulated inflammation and tissue cell apoptosis in kidneys by inactivating the NF-κB and MAPK pathways.

摘要

背景

肾脏中的过度炎症和细胞凋亡是急性肾损伤(AKI)发病机制中的关键因素。香豆素是一种天然黄酮类化合物,具有抗炎、抗凋亡和抗氧化作用。因此,我们研究了香豆素在AKI发生发展中的作用及机制。

方法

用脂多糖(LPS)诱导AKI小鼠,在LPS攻击1小时后,给小鼠口服香豆素或赋形剂。通过检测血清中的血尿素氮和肌酐来评估肾功能。用苏木精和伊红染色确定组织学变化。用TUNEL染色检测肾组织中的凋亡细胞。通过蛋白质免疫印迹法和逆转录定量聚合酶链反应(RT-qPCR)测量基因表达。

结果

香豆素减轻了LPS诱导的小鼠肾功能障碍和组织学缺陷。此外,香豆素抑制了LPS诱导的AKI小鼠肾脏中的过度炎症和组织凋亡。机制上,香豆素阻断了LPS诱导的AKI小鼠中核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路的激活。

结论

香豆素通过使NF-κB和MAPK信号通路失活,减轻了LPS刺激的肾脏炎症和组织细胞凋亡。

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