中国血液净化

中国血液净化 ›› 2025, Vol. 24 ›› Issue (01): 44-48.doi: 10.3969/j.issn.1671-4091.2025.01.009

• 基础研究 • 上一篇    下一篇

血液透析滤过对急性重症胰腺炎模型肠损伤及kelch样ECH相关蛋白1/核转录因子红系2相关因子2信号通路的影响

徐海平    李秀丽    暴 宇    杨 琛   

  1. 061000 沧州，1沧州市中心医院肾内二科
  • 收稿日期:2024-05-10 修回日期:2024-10-16 出版日期:2025-01-12 发布日期:2025-01-12
  • 通讯作者: 徐海平 E-mail:seelaez51521@21cn.com
  • 基金资助:
    河北省沧州市重点研究计划项目(213106045)

Effect of hemodiafiltration on intestinal injury and Keap1/Nrf2 signaling pathway in an animal model of acute severe pancreatitis#br#

XU Hai-ping, LI Xiu-li, BAO Yu, YANG Chen   

  1. Department of Nephrology, Cangzhou Central Hospital, Cangzhou 061000, China
  • Received:2024-05-10 Revised:2024-10-16 Online:2025-01-12 Published:2025-01-12
  • Contact: 061000 沧州，1沧州市中心医院肾内二科 E-mail:seelaez51521@21cn.com

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摘要： 的  探讨血液透析滤过(hemodiafiltration，HDF)对重症急性胰腺炎(severe acute pancreatitis，SAP)大鼠回肠损伤kelch样ECH相关蛋白1(kelch-like ECH-associated protein 1，Keap1)/核转录因子红系2相关因子2(nuclear factor erythroid 2-related factor 2，Nrf2)信号通路的影响。 方法 SD大鼠随机分为假手术组(n=18)、SAP组(n=18)和HDF组(n=18)。假手术组只进行开腹手术；SAP组和血液透析滤过组制备模型，血液透析滤过组在制备模型后立即行12 h的血液透析滤过治疗。手术后检测各组大鼠肠黏膜上皮细胞凋亡因子[BCL2相关X蛋白(BCL2-associated X，Bax)、B细胞淋巴瘤/白血病-2(B-cell lymphoma-2，Bcl-2)]的表达、门静脉血浆内毒素含量、细菌培养情况以及Keap1/Nrf2信号通路相关蛋白的表达。 结果 与假手术组相比，SAP组大鼠手术后肠黏膜上皮细胞中Bax表达提高(t=8.083，P=0.001)，Bcl-2表达降低(t=4.765，P=0.008)。与假手术组相比，SAP组血浆内毒素含量(12小时：t=15.110，P＜0.001；24小时：t=19.050，P＜0.001；48小时：t=18.330，P＜0.001)以及胰腺(12小时：t=23.712，P＜0.001；24小时：t=20.901，P＜0.001；48小时：t=36.740，P＜0.001)、肝脏(12小时：t=23.983，P＜0.001；24小时：t=29.692，P＜0.001；48小时：t=35.694，P＜0.001)中细菌培养阳性率提高。与SAP组相比，HDF组大鼠手术后肠黏膜上皮细胞中Bax表达降低(t=6.796，P=0.002)，Bcl-2表达提高(t=5.825，P=0.004)；血浆内毒素含量(12小时：t=6.235，P=0.003；24小时：t=12.251，P＜0.001；48小时：t=12.980，P＜0.001)以及胰腺(12小时：t=16.470，P＜0.001；24小时：t=5.950，P=0.004；48小时：t=15.071，P＜0.001)、肝脏(12小时：t=2.782，P=0.049；24小时：t=9.790，P＜0.001；48小时：t=15.172，P＜0.001)中细菌培养阳性率降低。与假手术组相比，SAP组大鼠Keap1(t=11.611，P＜0.001)和Nrf2(t=12.241，P＜0.001)的表达降低。与SAP组相比，HDF组大鼠Keap1(t=80.658，P=0.001)和Nrf2(t=12.312，P＜0.001)的表达提高。 结论 HDF能够抑制急性重症胰腺炎大鼠肠上皮细胞通透性，有效改善肠功能障碍，并具有抑制内毒素与细菌移位的功能。

关键词: 血液透析滤过, 急性重症胰腺炎, Keap1/Nrf2信号通路, 粘膜上皮细胞

Abstract: Objective  To investigate the effect of hemodiafiltration (HDF) on the intestinal injury of severe acute pancreatitis (SAP) rats and the Keap1/Nrf2 signaling pathway.  Methods  Sprague-Dawley (SD) rats were randomly divided into sham operation group (n=18), SAP group (n=18) and HDF group (n=18). Open surgery without SAP manipulation was performed in sham operation group, SAP model was performed in SAP group and HDF group, and continuous HDF for 12 hours was conducted immediately after the preparation of SAP model in HDF group. The expressions of apoptotic factors Bax and Bcl-2,  Keap1/Nrf2 signaling pathway-related proteins in intestinal epithelial cells, endotoxin level in plasma of portal vein, and bacterial culture were assayed after the operation.  Results  In SAP group, the expression of Bax in intestinal epithelial cells was higher than that in sham operation group (t=8.083, P=0.001), while the expression of Bcl-2 in intestinal epithelial cells was lower than that in sham operation group (t=4.765, P=0.008); plasma endotoxin of portal vein and positive rates of bacterial culture of pancreas and liver were higher than those in sham operation group (plasma endotoxin at 12h: t=15.110, P＜0.001; at 24h: t=19.050, P＜0.001; at 48h: t=18.330, P＜0.001. positive bacterial culture of pancreas at 12h: t=23.712, P＜0.001; at 24h: t=20.901, P＜0.001; at 48h: t=36.740, P＜0.001. positive bacterial culture of liver at 12h: t=23.983, P＜0.001; at 24h: t=29.692, P＜0.001; at 48h: t=35.694, P＜0.001). In HDF group, the expression of Bcl-2 in intestinal epithelial cells was higher than that in SAP group (t=5.825, P=0.004); the expression of Bax in intestinal epithelial cells, plasma endotoxin of portal vein and positive rates of bacterial culture of pancreas and liver were lower than those in SAP group (Bax: t=6.796, P=0.002. plasma endotoxin at 12h: t=6.235, P=0.003; at 24h: t=12.251, P＜0.001; at 48h: t=12.980, P＜0.001. positive bacterial culture of pancreas at 12h: t=16.470, P＜0.001; at 24h: t=5.950, P=0.004; at 48h: t=15.071, P＜0.001. positive bacterial culture of liver at 12h: t=2.782, P=0.049; at 24h: t=9.790, P＜0.001; at 48h: t=15.172, P＜0.001). In SAP group, the expressions of Keap1 and Nrf2 were lower than those in sham operation group (Keap1: t=11.611, P＜0.001; Nrf2: t=12.241, P＜0.001). In HDF group, the expressions of Keap1 and Nrf2 were higher than those in SAP group (Keap1: t=80.658, P=0.001; Nrf2: t=12.312, P=0.000).  Conclusion  Continuous HDF can improve the permeability of intestinal epithelial cells and intestinal dysfunction, and inhibit endotoxin and bacterial translocation in SAP rats.

Key words: Continuous hemodiafiltration, Severe acute pancreatitis, Keap1/Nrf2 pathway, Mucosal epithelial cells

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