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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摘要 目的: 探索乌司他丁是否可以通过抑制铁死亡减轻重症急性胰腺炎模型的急性肾损伤。方法: 24只成熟的Wistar雄性大鼠随机分为4组,每组6只:对照组(Control),重症急性胰腺炎组(SAP),重症急性胰腺炎组+低剂量乌司他丁组(SAP+UTI-L),重症急性胰腺炎组+高剂量乌司他丁组(SAP+UTI-H)。H&E染色评估肾小管的组织学变化,根据BUN和SCr含量对肾功能进行评估,ELISA试剂盒检测TNF-α、IL-6、SOD、H₂O₂、MDA、ROS、GPX4活性的水平。铁含量检测试剂盒测定肾脏组织中铁水平,Western blot和qRT-PCR分别检测ACSL4,GPx4,FTH1的蛋白表达水平和mRNA水平。结果: 与Control组相比,SAP组的肾组织损伤评分明显升高,且SCr和BUN水平显著增加(P<0.05),TNF-α和IL-6水平以及MDA,H₂O₂和ROS的水平显著增加(P<0.01),肾铁浓度显著增加(P<0.01),GPX4活性显著降低(P<0.01),铁死亡相关蛋白GPX4和FTH1蛋白表达水平和mRNA水平明显降低(P<0.01),ACSL4的蛋白表达水平和mRNA水平明显升高(P<0.01),经乌司他丁治疗后,肾组织损伤评分显著降低,Cr(P<0.05)和BUN(P<0.01)水平明显下降,炎症反应和氧化应激水平下降,肾铁浓度明显降低,GPX4活性,GPX4和FTH1蛋白表达水平及mRNA水平明显升高,ACSL4的蛋白表达水平和mRNA水平显著降低。结论: 乌司他丁通过抑制铁死亡减轻重症急性胰腺炎大鼠模型的急性肾损伤。

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关键词 ：胰腺炎, 乌司他丁, 铁死亡, 肾损伤

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

基金资助:河北省2020年度医学科学研究课题计划项目,(编号:20200453)

通讯作者: 苏静

引用本文:

周少英, 王玉梅, 刘博, 杨珍, 李欢欢, 陈志飞, 苏静. 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[J]. 河北医学, 2024, 30(2): 194-199.
ZHOU Shaoying, et al. Ulinastatin Alleviates Acute Kidney Injury in Severe Acute Pancreatitis Models by Inhibiting Ferroptosis. HeBei Med, 2024, 30(2): 194-199.

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

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