南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (2): 286-292.doi: 10.12122/j.issn.1673-4254.2022.02.17

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CaMK Ⅱ在小鼠重症急性胰腺炎胰腺损伤中的作用

蒋 文，吴 俊，曽佳容，景光旭，汤礼军，孙红玉   

  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，西部战区总医院基础医学实验室，四川 成都 610083
  • 出版日期:2022-02-20 发布日期:2022-03-16

Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis

JIANG Wen, WU Jun, ZENG Jiarong, JING Guangxu, TANG Lijun, SUN Hongyu   

  1. College of Medicine Southwest Jiaotong University, Chengdu 610063, China; PLA Center of General Surgery, Pancreatic Injury and Repair Key Laboratory of Sichuan Province, General Hospital of Western Theater Command, Chengdu 610083, China; Basic Medical Laboratory, General Hospital of Western Theater Command, Chengdu 610083, China
  • Online:2022-02-20 Published:2022-03-16

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摘要： 目的 观察钙调素依赖蛋白激酶（CaMK Ⅱ）在重症急性胰腺炎（SAP）小鼠胰腺组织中的表达情况，并探讨其抑制剂KN93对SAP胰腺损伤的保护作用和机制。方法 36只健康雄性C57小鼠随机分为假手术组、SAP组、KN93组、SAP组+KN93组，9只/组。于造模后24 h收集血清和胰腺组织；采用HE染色观察胰腺组织病理改变；Elisa检测血清脂肪酶、淀粉酶活性以及炎性因子变化情况；免疫印迹法检测CaMK Ⅱ、p-CaMK Ⅱ、p-NF-κB、MAPK、p-MAPK在小鼠胰腺组织中的表达变化。 结果 与假手术组比较，SAP组p-CaMK Ⅱ、p-NF-κB、p-MAPK表达水平升高（P<0.05）。KN93干预后，SAP小鼠胰腺组织病理损伤减轻，血清脂肪酶、淀粉酶以及炎性因子（TNF-α、IL-6）水平降低（P<0.05），同时NF-κB、ERK和MAPK蛋白磷酸化也降低（P<0.05）。结论 CaMK Ⅱ蛋白在SAP疾病胰腺组织活性升高，CaMK Ⅱ抑制剂KN93能有效减轻SAP小鼠胰腺损伤和炎症程度，其机制可能与ERK/MAPK信号通路有关。

关键词: 重症急性胰腺炎；CaMK Ⅱ；NF-κB；KN93

Abstract: Objective To investigate the expression of Ca2 +/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMKⅡ inhibitor, against pancreatic injury in SAP and the possible mechanism. Methods Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMKⅡ, p-CaMKⅡ, p-NF-κB, MAPK and p-MAPK in mouse pancreas. Results Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P<0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P<0.05). Conclusion The activity of CaMKⅡ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Key words: severe acute pancreatitis; CaMKⅡ; nuclear factor-κB; KN93