Role of ATP citrate lyase in pancreatic injury during acute pancreatitis and its action mechanism
10.7659/j.issn.1005-6947.2024.12.011
- VernacularTitle:ATP柠檬酸裂解酶在急性胰腺炎胰腺损伤中的作用与机制
- Author:
Xin YAN
1
;
Qingzhu DING
1
;
Yupu HONG
1
Author Information
1. 福建医科大学附属第一医院肝胆胰外科,福建福州 350005;福建医科大学附属第一医院滨海院区国家区域医疗中心肝胆胰外科,福建福州 350212;福建省腹部外科研究所,福建福州 350005
- Publication Type:Journal Article
- Keywords:
Pancreatitis;
ATP Citrate Lyase;
Inflammation;
NF-κB
- From:
Chinese Journal of General Surgery
2024;33(12):2030-2037
- CountryChina
- Language:Chinese
-
Abstract:
Background and Aims:ATP citrate lyase (Acly) is widely expressed in various tissues and has been shown to play a crucial role in many inflammatory diseases. However,the role of Acly in acute pancreatitis (AP)-induced pancreatic injury remains unclear. This study was conducted to investigate the effect of Acly on pancreatic injury in a mouse AP model and to preliminarily explore its underlying mechanism.Methods:Twelve male C57BL6/J AclycKO mice (conditional pancreatic Acly knockout) and twelve Aclywt mice (with intact pancreatic Acly expression) were randomly divided into AP groups (administered caerulein at 100 μg/kg intraperitoneally,6 times/d,with 1-hour intervals,for 4 consecutive days) and control groups (administered saline in the same manner),with six AclycKO mice and six Aclywt mice in each group. Pancreatic tissue samples were collected 24 hours after modeling to observe pathological changes in the pancreas and to measure the expression of the macrophage marker CD68,the neutrophil marker myeloperoxidase (MPO),as well as nuclear factor NF-κB p65,Toll-like receptor 4 (TLR4),and pro-inflammatory factors TNF-α and IL-1β.Results:Compared with the control group,the AP group exhibited significant pathological changes in the pancreas. The pathological damage in AclycKO mice was more severe than in that in Aclywt mice,with significantly higher inflammation and necrosis of pancreatic tissue scores in AclycKO mice (all P<0.05). In the AP group,the pancreatic expressions of CD68 and MPO were significantly higher in AclycKO mice than those in Aclywt mice (both P<0.05). Additionally,AclycKO mice showed increased nuclear positivity for NF-κB p65 and elevated expression of TLR4,TNF-α,and IL-1β compared with Aclywt mice (all P<0.05). Conclusion:Acly exerts a protective effect against AP-induced pancreatic injury,possibly by inhibiting the activation of the NF-κB signaling pathway,thereby mitigating the inflammatory response.
