Liu Qiang, Gu Xinyi, Liu Xiaodie, Gu Ye, Zhang Hongchen, Yang Jianfeng, Huang Zhicheng
Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310058, China.
Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310058, China.
Heliyon. 2024 May 22;10(11):e31296. doi: 10.1016/j.heliyon.2024.e31296. eCollection 2024 Jun 15.
Acute pancreatitis (AP) is an inflammatory disease characterized by localized pancreatic injury and a systemic inflammatory response. Fatty acids (FAs), produced during the breakdown of triglycerides (TGs) in blood and peripancreatic fat, escalate local pancreatic inflammation to a systemic level by damaging pancreatic acinar cells (PACs) and triggering M1 macrophage polarization. This paper provides a comprehensive analysis of lipases' roles in the onset and progression of AP, as well as the effects of long-chain fatty acids (LCFAs) on the function of pancreatic acinar cells (PACs). Abnormalities in the function of PACs include Ca overload, premature trypsinogen activation, protein kinase C (PKC) expression, endoplasmic reticulum (ER) stress, and mitochondrial and autophagic dysfunction. The study highlights the contribution of long-chain saturated fatty acids (LC-SFAs), especially palmitic acid (PA), to M1 macrophage polarization through the activation of the NLRP3 inflammasome and the NF-κB pathway. Furthermore, we investigated lipid lowering therapy for AP. This review establishes a theoretical foundation for pro-inflammatory mechanisms associated with FAs in AP and facilitating drug development.
急性胰腺炎（AP）是一种以胰腺局部损伤和全身炎症反应为特征的炎症性疾病。血液和胰腺周围脂肪中甘油三酯（TGs）分解过程中产生的脂肪酸（FAs），通过损伤胰腺腺泡细胞（PACs）和触发M1巨噬细胞极化，将局部胰腺炎症升级到全身水平。本文全面分析了脂肪酶在AP发病和进展中的作用，以及长链脂肪酸（LCFAs）对胰腺腺泡细胞（PACs）功能的影响。胰腺腺泡细胞（PACs）功能异常包括钙超载、胰蛋白酶原过早激活、蛋白激酶C（PKC）表达、内质网（ER）应激以及线粒体和自噬功能障碍。该研究强调了长链饱和脂肪酸（LC-SFAs），尤其是棕榈酸（PA），通过激活NLRP3炎性小体和NF-κB途径对M1巨噬细胞极化的作用。此外，我们还研究了AP的降脂治疗。这篇综述为AP中与脂肪酸相关的促炎机制及促进药物开发奠定了理论基础。
