Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor

Molecular Medicine

Research Article

Jingyi Chen¹  Zhihua Ruan¹  Xiaofang Gong¹  Liangzhi Xiong¹  Yu Wang¹  Shuang Wang¹  Chengyi Wu¹  Hui Shang²  Yanrong Luo³ 

[1] Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei, China;Department of Orthopaedic, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei, China;Physical examination center, Shiyan Hospital of Integrated Traditional and Western Medicine, 442000, Shiyan, Hubei, China;

关键词: Sepsis;    Acute liver injury;    Indole-3-propionic acid;    Pregnane X receptor;    Gut microbiota;   

DOI  :  10.1186/s10020-023-00658-x

 received in 2023-01-13, accepted in 2023-04-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe morbidity and mortality of sepsis are extremely high, which is a major problem plaguing human health. However, current drugs and measures for the prevention and treatment of sepsis have little effect. Sepsis-associated acute liver injury (SALI) is an independent risk factor for sepsis, which seriously affects the prognosis of sepsis. Studies have found that gut microbiota is closely related to SALI, and indole-3-propionic Acid (IPA) can activate Pregnane X receptor (PXR). However, the role of IPA and PXR in SALI has not been reported.MethodsThis study aimed to explore the association between IPA and SALI. The clinical data of SALI patients were collected and IPA level in feces was detected. The sepsis model was established in wild-type mice and PXR knockout mice to investigate the role of IPA and PXR signaling in SALI.ResultsWe showed that the level of IPA in patients’ feces is closely related to SALI, and the level of IPA in feces has a good ability to identify and diagnose SALI. IPA pretreatment significantly attenuated septic injury and SALI in wild-type mice, but not found in knockout PXR gene mice.ConclusionsIPA alleviates SALI by activating PXR, which reveals a new mechanism of SALI, and provides potentially effective drugs and targets for the prevention of SALI.

【 授权许可】

CC BY   
© The Author(s) 2023

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