南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (4): 561-567.doi: 10.12122/j.issn.1673-4254.2022.04.12

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腹腔穿刺引流术通过激活Nrf-2/HO-1通路和抑制自噬减轻大鼠重症急性胰腺炎

卢一琛，吴 俊，蒋 文，刘江涛，且华吉，孙红玉，汤礼军   

  1. 西南交通大学医学院，四川 成都 610063；西部战区总医院全军普通外科中心//四川省胰腺损伤与修复重点实验室，四川 成都 610083
  • 出版日期:2022-04-20 发布日期:2022-04-29

Abdominal puncture drainage alleviates severe acute pancreatitis in rats by activating Nrf-2/HO-1 pathway and promoting autophagy

LU Yichen, WU Jun, JIANG Wen, LIU Jiangtao, QIE Huaji, SUN Hongyu, TANG Lijun   

  1. School of Clinical Medicine, Southwest Jiaotong University, Chengdu 610063, China; Center of General Surgery//Sichuan Provincial Key Laboratory of Pancreatic Injury and Repair, General Hospital of Western Theater Command, Chengdu 610083, China
  • Online:2022-04-20 Published:2022-04-29

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摘要： 目的 探讨早期腹腔穿刺引流术（APD）对大鼠重症急性胰腺炎（SAP）自噬及Nrf-2/HO-1通路的影响及其可能机制。方法 将32只SD大鼠随机分为假手术组（SO组，n=8），重症急性胰腺炎组（SAP组，n=8，4%牛磺胆酸钠逆行注射法），腹腔穿刺引流术组（APD组，n=8，SAP造模后于右下腹置管引流），APD+HO-1特异性抑制剂组（APD+ZnPP组，n=8，APD造模前12 h腹腔注射30 mg/kg ZnPP）。造模后12 h采集大鼠血样及胰腺组织。以HE染色评价胰腺组织病理改变，全自动生化分析仪检测血清中淀粉酶、脂肪酶水平，ELISA法检测血清炎症因子水平，比色法检测胰腺组织内氧化应激水平，透射电镜下观察胰腺腺泡细胞内亚细胞器结构及自噬改变，RT-PCR及Western blotting检测自噬相关蛋白及Nrf-2/HO-1通路蛋白的表达。结果 与SAP组相比，APD组大鼠胰腺组织病理损伤显著减轻（P<0.05），血清淀粉酶、脂肪酶及肿瘤坏死因子α（TNF-α）、白介素1-β（IL-1β）水平明显下降（P<0.05），胰腺组织内氧化应激水平显著下降（P<0.05），并伴有Nrf-2/HO-1通路的激活（P<0.05）。ZnPP可以抑制上述的治疗作用。同时，APD干预可逆转SAP造成的线粒体、内质网损伤，并减少p62积累（P<0.05），抑制腺泡细胞内自噬受损。结论 早期APD引流治疗可通过激活Nrf-2/HO-1通路减轻局部氧化应激、修复受损自噬进而降低SAP的严重程度。

关键词: 重症急性胰腺炎；腹腔穿刺引流术；自噬；血红素加氧酶-1

Abstract: Objective To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism. Methods Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting. Results Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP. Conclusion APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP

Key words: severe acute pancreatitis; abdominal puncture drainage; autophagy; heme oxygenase-1