Li Huangen, Gao Yi, Huang Minglian, Zhang Hongling, Wu Qingqing, Huang Youpei, Ye Xiaotong, Chen Weiwen
Department of Critical Care Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
Department of General Medicine, Xiamen Changgeng Hospital Affiliated to Huaqiao University, Xiamen, China.
Front Pharmacol. 2025 Apr 23;16:1557681. doi: 10.3389/fphar.2025.1557681. eCollection 2025.
Tetramethylpyrazine (TMPZ), an active alkaloid derived from traditional Chinese medicine, has shown anti-inflammatory and anti-pyroptotic properties. However, its role in acute pancreatitis (AP)-induced pyroptosis remains unclear. This study aims to investigate the effects of TMPZ on AP-induced pyroptosis and its potential mechanisms.
A cerulein-induced AP rat model was used to evaluate TMPZ's protective effects , and its mechanisms were explored using AR42J cells . Pancreatic injury was assessed by hematoxylin-eosin staining, TUNEL assay, and serum biochemistry. Transmission electron microscopy, immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to examine pyroptosis and related signaling pathways. Cytotoxicity and apoptosis were measured by CCK-8, LDH assays, and Hoechst 33342/PI staining. The role of NRF2 in TMPZ's effects was further evaluated using NRF2 siRNA.
TMPZ alleviated pancreatic histopathological damage, reduced apoptosis, and decreased serum amylase levels and pro-inflammatory cytokines (IL-1β, IL-18). TMPZ also suppressed pyroptosis by inhibiting NLRP3 inflammasome activation and downregulating pyroptosis-related proteins (NLRP3,caspase-1, ASC, GSDMD) while upregulating NRF2 and HO-1 expression. NRF2 siRNA attenuated TMPZ's anti-inflammatory and pyroptosis-inhibitory effects, confirming the involvement of the NRF2 pathway.
TMPZ mitigates AP-induced inflammation and injury by modulating pyroptosis via the NRF2 signaling pathway. These findings suggest TMPZ's therapeutic potential for AP.
川芎嗪（TMPZ）是一种源自中药的活性生物碱，已显示出抗炎和抗焦亡特性。然而，其在急性胰腺炎（AP）诱导的焦亡中的作用仍不清楚。本研究旨在探讨TMPZ对AP诱导的焦亡的影响及其潜在机制。
采用雨蛙素诱导的AP大鼠模型评估TMPZ的保护作用，并使用AR42J细胞探索其机制。通过苏木精-伊红染色、TUNEL检测和血清生化评估胰腺损伤。进行透射电子显微镜、免疫荧光、蛋白质印迹和定量实时聚合酶链反应（RT-qPCR）以检测焦亡和相关信号通路。通过CCK-8、LDH检测和Hoechst 33342/PI染色测量细胞毒性和凋亡。使用NRF2 siRNA进一步评估NRF2在TMPZ作用中的作用。
TMPZ减轻了胰腺组织病理学损伤，减少了细胞凋亡，并降低了血清淀粉酶水平和促炎细胞因子（IL-1β、IL-18）。TMPZ还通过抑制NLRP3炎性小体激活和下调焦亡相关蛋白（NLRP3、caspase-1、ASC、GSDMD）来抑制焦亡，同时上调NRF2和HO-1表达。NRF2 siRNA减弱了TMPZ的抗炎和焦亡抑制作用，证实了NRF2途径的参与。
TMPZ通过NRF2信号通路调节焦亡来减轻AP诱导的炎症和损伤。这些发现表明TMPZ对AP具有治疗潜力。
