Wenquan Zhang , Min Du , Yingjian Jiang , Jiang Wang , Yue Yu , DianLiang Zhang
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引用次数: 0
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.
背景：重症急性胰腺炎（SAP）是临床上常见的消化系统疾病，重症急性胰腺炎患者往往伴有肝损伤。一些研究表明，热蛋白沉积在重症急性胰腺炎（SAP）后的肝损伤中起一定作用。然而，其确切机制仍不清楚。本研究旨在阐明 SAP 后肝损伤与热蛋白沉积之间的关联和具体机制，为 SAP 诱导肝损伤的研究提供理论支持：方法：成功建立了伴有肝损伤的 SAP 大鼠模型。方法：成功建立了伴有肝损伤的 SAP 大鼠模型，并利用定量反转录聚合酶链反应（qRT-PCR）对不同肝组织组 miR-103-3p 的表达水平进行了定量分析。生物信息学分析和双荧光素酶报告实验证实，NLRP1 是 miR-103-3p 的直接靶标。研究人员对 miR-103-3p 的水平进行了体内评估，并通过 Western 印迹、qRT-PCR、扫描电子显微镜、组织病理学、免疫荧光和免疫组织化学等方法评估了 SAP 后肝损伤过程中细胞热解的程度。研究验证了 miR-103-3p 在调控 NLRP1 介导的热蛋白沉积中的作用及其对 SAP 诱导的肝损伤的影响：结果：本研究发现，SAP 诱导的肝损伤后，肝组织中 miR-103-3p 的表达明显降低，细胞裂解参与了肝损伤的过程。实验验证表明，NLRP1是miR-103-3p的下游靶标。在体外过表达 miR-103-3p 能明显减轻 SAP 损伤后肝损伤的严重程度，同时抑制细胞嗜热：这些研究结果表明，肝细胞脓毒症可能与 SAP 诱导的肝损伤有关，而 miR-103-3p 可通过抑制 NLRP1 的表达减轻肝损伤，从而缓解肝细胞脓毒症。
期刊介绍：
Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted
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