Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
Physical examination center, Shiyan Hospital of Integrated Traditional and Western Medicine, Shiyan, 442000, Hubei, China.
Mol Med. 2023 May 19;29(1):65. doi: 10.1186/s10020-023-00658-x.
The 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.
This 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.
We 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.
IPA alleviates SALI by activating PXR, which reveals a new mechanism of SALI, and provides potentially effective drugs and targets for the prevention of SALI.
脓毒症的发病率和死亡率极高，是严重威胁人类健康的难题之一。然而，目前脓毒症的预防和治疗药物及措施效果甚微。脓毒症相关性急性肝损伤（SALI）是脓毒症的独立危险因素，严重影响脓毒症的预后。研究发现肠道微生物群与 SALI 密切相关，吲哚-3-丙酸（IPA）可以激活孕烷 X 受体（PXR）。然而，IPA 和 PXR 在 SALI 中的作用尚未报道。
本研究旨在探讨 IPA 与 SALI 之间的关系。收集 SALI 患者的临床资料并检测粪便中 IPA 水平。在野生型小鼠和 PXR 基因敲除小鼠中建立脓毒症模型，以研究 IPA 和 PXR 信号通路在 SALI 中的作用。
我们发现患者粪便中 IPA 水平与 SALI 密切相关，粪便中 IPA 水平对 SALI 具有良好的识别和诊断能力。IPA 预处理可显著减轻野生型小鼠的脓毒症损伤和 SALI，但在敲除 PXR 基因的小鼠中未发现。
IPA 通过激活 PXR 减轻 SALI，揭示了 SALI 的新机制，为 SALI 的预防提供了有潜在作用的药物和靶点。
