乌司他丁通过抑制铁死亡减轻重症急性胰腺炎模型的急性肾损伤

doi:10.3969/j.issn.1006-6233.2024.02.04

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Abstract Objective: To investigate whether Ulinastatin can reduce acute kidney injury in severe acute pancreatitis models by inhibiting ferroptosis. Methods: A total of 24 mature male Wistar rats were randomly divided into 4 groups with 6 rats in each group: The histological changes of renal tubule in Control group (Control), severe acute pancreatitis group (SAP), severe acute pancreatitis group + low-dose Ulinastatin group (SAP+UTI-L), severe acute pancreatitis group + high-dose Ulinastatin group (SAP+UTI-H) were evaluated by H&E staining, and renal function was evaluated according to BUN and SCr content. The activity levels of TNF-α, IL-6, SOD, H2O2, MDA, ROS and GPX4 were detected by ELISA kit. Iron content detection kit was used to determine iron levels in kidney tissues. Western blot and qRT-PCR were used to detect the protein expression levels and mRNA levels of ACSL4, GPx4 and FTH1, respectively. Results: Compared with Control group, the renal tissue injury score in SAP group was significantly increased, SCr and BUN levels were significantly increased (P<0.05), TNF-α and IL-6 levels, MDA, H₂O₂ and ROS levels were significantly increased (P<0.01), and renal iron concentration was significantly increased (P<0.01). The activity of GPX4 was significantly decreased (P<0.01), the protein expression levels and mRNA levels of iron death related proteins GPX4 and FTH1 were significantly decreased (P<0.01), and the protein expression levels and mRNA levels of ACSL4 were significantly increased (P<0.01). After Ulinastatin treatment, the renal tissue injury score was significantly decreased. The levels of Cr (P<0.05) and BUN (P<0.01) were significantly decreased, the levels of inflammation and oxidative stress were decreased, the concentration of renal iron was significantly decreased, the activity of GPX4, the expression levels of GPX4 and FTH1 protein and mRNA levels were significantly increased, and the protein expression levels and mRNA levels of ACSL4 were significantly decreased. Conclusion: Ulinastatin can reduce acute kidney injury in rats with severe acute pancreatitis by inhibiting ferroptosis.

Key words： Pancreatitis Ulinastatin Ferroptosisl Kidney injury

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.02.04 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I2/194

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