miR-103-3p 通过 miR-103-3p/NLRP1 轴抑制细胞焦亡减轻重症急性胰腺炎肝损伤

miR-103-3p attenuates liver injury with severe acute pancreatitis by inhibiting pyroptosis through miR-103-3p/NLRP1 axis.

机构信息

Affiliation: Medical College of Qingdao University, Qingdao University, Qingdao, Shandong Province 266071, China.

Gastrointestinal surgery department, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong, China.

出版信息

Acta Histochem. 2024 Dec;126(8):152211. doi: 10.1016/j.acthis.2024.152211. Epub 2024 Oct 30.

DOI:10.1016/j.acthis.2024.152211

PMID:39476479

Abstract

BACKGROUND

Severe acute pancreatitis (SAP) is a common digestive system disorder in clinical practice, and it is often associated with liver damage in patients with severe acute pancreatitis. Several studies have indicated that pyroptosis plays a role in liver damage following severe acute pancreatitis (SAP). However, the precise mechanisms remain unclear. This study aims to elucidate the association and specific mechanisms between liver injury following SAP and pyroptosis, providing theoretical support for research on SAP-induced liver injury.

METHODS

A rat model of SAP with concomitant liver injury was successfully established. The expression levels of miR-103-3p across different liver tissue groups were quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Bioinformatic analyses and dual-luciferase reporter assays confirmed that NLRP1 is a direct target of miR-103-3p. In vivo assessments of miR-103-3p levels were performed, and the extent of cell pyroptosis during liver injury post-SAP was evaluated through western blotting, qRT-PCR, scanning electron microscopy, histopathology, immunofluorescence, and immunohistochemistry. The role of miR-103-3p in regulating NLRP1-mediated pyroptosis and its impact on SAP-induced liver injury were validated.

RESULTS

This study reports that following SAP-induced liver injury, the expression of miR-103-3p in liver tissue was significantly decreased, and cell pyroptosis was involved in the process of liver injury. Experimental validation indicated that NLRP1 was a downstream target of miR-103-3p. Overexpression of miR-103-3p in vitro significantly alleviated the severity of liver injury following SAP, while simultaneously inhibiting cell pyroptosis.

CONCLUSION

These findings indicate that pyroptosis may be linked to SAP-induced liver injury and that miR-103-3p mitigates hepatocyte pyroptosis by reducing liver injury through the suppression of NLRP1 expression.

摘要

背景

严重急性胰腺炎（SAP）是临床实践中常见的消化系统疾病，且常伴有重症急性胰腺炎患者的肝损伤。几项研究表明，细胞焦亡在重症急性胰腺炎（SAP）后肝损伤中发挥作用。然而，确切的机制尚不清楚。本研究旨在阐明 SAP 后肝损伤与细胞焦亡之间的关联和具体机制，为 SAP 诱导的肝损伤研究提供理论支持。

方法

成功建立了伴有肝损伤的 SAP 大鼠模型。采用定量逆转录聚合酶链反应（qRT-PCR）检测不同肝组织中 miR-103-3p 的表达水平。生物信息学分析和双荧光素酶报告基因实验证实 NLRP1 是 miR-103-3p 的直接靶基因。进行 miR-103-3p 水平的体内评估，并通过 Western blot、qRT-PCR、扫描电子显微镜、组织病理学、免疫荧光和免疫组化评估 SAP 后肝损伤时细胞焦亡的程度。验证 miR-103-3p 在调节 NLRP1 介导的细胞焦亡中的作用及其对 SAP 诱导的肝损伤的影响。