Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong Province, China.
Wuxi School of Medicine, Jiangnan University, Wuxi 214000, Jiangsu Province, China.
World J Gastroenterol. 2023 Apr 21;29(15):2294-2309. doi: 10.3748/wjg.v29.i15.2294.
Ferroptosis is involved in developing inflammatory diseases; yet, its role in acute hypertriglyceridemic pancreatitis (HTGP) remains unclear.
To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms.
An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein (CAE). Then, pancreatic tissues from the model animals were subjected to proteome sequencing analysis. The pathological changes and scores of the pancreas, lung, and kidney were determined using hematoxylin-eosin staining. The levels of serum amylase (AMY), triglyceride, and total cholesterol were measured with an automatic blood cell analyzer. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were determined by enzyme linked immunosorbent assay. Malonaldehyde (MDA), glutathione (GSH), and Fe were detected in the pancreas. Finally, immunohistochemistry was performed to assess the expression of ferroptosis-related proteins.
Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase (NOX) 2 may participate in ferroptosis regulation. Moreover, the levels of serum AMY, TNF-α, IL-6, and IL-1β were significantly increased, MDA and Fe were upregulated, GSH and ferroptosis-related proteins were reduced, and the injury of the pancreas, lung, and kidney were aggravated in the P407 + CAE group compared to CAE and wild type groups (all < 0.05). Notably, the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α, IL-6, and IL-1β in the serum of the mice.
Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.
铁死亡与炎症性疾病的发生发展有关；然而，其在急性高脂血症性胰腺炎（HTGP）中的作用尚不清楚。
探讨铁死亡是否参与 HTGP 的发生过程，并阐明其潜在机制。
采用腹腔注射 P-407 和 CAE 诱导 HTGP 小鼠模型。然后，对模型动物的胰腺组织进行蛋白质组测序分析。采用苏木精-伊红染色法检测胰腺、肺和肾的病理变化和评分。采用自动血细胞分析仪测定血清淀粉酶（AMY）、甘油三酯和总胆固醇水平。此外，采用酶联免疫吸附试验测定血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-1β水平。检测胰腺组织中丙二醛（MDA）、谷胱甘肽（GSH）和铁的含量。最后，通过免疫组织化学法评估铁死亡相关蛋白的表达。
蛋白质组测序结果显示，铁死亡参与 HTGP 的发生过程，NADPH 氧化酶（NOX）2 可能参与铁死亡的调节。此外，与 CAE 组和野生型组相比，P407+CAE 组血清 AMY、TNF-α、IL-6 和 IL-1β水平显著升高，MDA 和 Fe 上调，GSH 和铁死亡相关蛋白减少，胰腺、肺和肾损伤加重（均<0.05）。值得注意的是，铁死亡和 NOX2 的抑制减轻了小鼠血清中 TNF-α、IL-6 和 IL-1β的释放及其导致的病理损伤。
铁死亡在 HTGP 中具有重要作用，可能成为临床治疗的潜在靶点。
