Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway

DAI Jingjing; WANG Zhao; TANG Qi

doi:10.6039/j.issn.1001-0408.2024.14.08

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Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway

更新时间：2024-07-25

- Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway
- ZHONGGUO YAOFANG Vol. 35, Issue 14, Pages: 1722-1726(2024)
- 作者机构：
  
  遵义市第一人民医院（遵义医科大学第三附属医院）重症医学科，贵州遵义　563000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.14.08
  CLC： R965
- Published：30 July 2024，
  
  Received：29 November 2023，
  
  Revised：21 June 2024，
- 稿件说明：
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代静静,王兆,唐奇.益母草碱通过调节HMGB1/RAGE信号通路对重症急性胰腺炎大鼠的改善作用 ^Δ[J].中国药房,2024,35(14):1722-1726.

DAI Jingjing,WANG Zhao,TANG Qi.Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway[J].ZHONGGUO YAOFANG,2024,35(14):1722-1726.
代静静,王兆,唐奇.益母草碱通过调节HMGB1/RAGE信号通路对重症急性胰腺炎大鼠的改善作用 ^Δ[J].中国药房,2024,35(14):1722-1726. DOI： 10.6039/j.issn.1001-0408.2024.14.08.

DAI Jingjing,WANG Zhao,TANG Qi.Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway[J].ZHONGGUO YAOFANG,2024,35(14):1722-1726. DOI： 10.6039/j.issn.1001-0408.2024.14.08.

摘要

目的

研究益母草碱对重症急性胰腺炎（SAP）大鼠胰腺损伤的影响，并基于高迁移率族蛋白1（HMGB1）/晚期糖基化终产物受体（RAGE）信号通路探讨其作用机制。

方法

采用胰胆管注射5%牛磺胆酸钠构建SAP大鼠模型，造模成功的大鼠随机分为模型组、低剂量益母草碱组（8 mg/kg）、高剂量益母草碱组（16 mg/kg）、HMGB1过表达组（8 μg/kg）、高剂量益母草碱+HMGB1过表达组（16 mg/kg益母草碱+8 μg/kg HMGB1），每组14只；另取14只大鼠作为假手术组。各组大鼠腹腔或尾静脉注射相应药物或生理盐水，每日1次，连续5 d。末次给药后，检测大鼠血清中淀粉酶（AMS）、脂肪酶（LPS）水平；观察其胰腺组织病理损伤；检测其胰腺组织中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平以及HMGB1、RAGE mRNA和蛋白表达水平。

结果

与模型组比较，低、高剂量益母草碱组大鼠胰腺组织结构逐渐恢复、炎症细胞浸润逐渐减少，病理损伤评分和AMS、LPS、TNF-α、IL-6、MDA水平以及HMGB1、RAGE mRNA和蛋白表达水平均显著降低，SOD水平均显著升高（

＜0.05），且高剂量益母草碱组改善效果更明显（

＜0.05）；HMGB1过表达组大鼠胰腺组织病理损伤加重，除SOD水平显著降低外，其余各指标均显著升高（

＜0.05）。HMGB1过表达可减弱高剂量益母草碱对SAP大鼠上述指标的改善效果（

＜0.05）。

结论

益母草碱可能通过抑制HMGB1/RAGE信号通路激活来减轻SAP大鼠的胰腺损伤和胰腺组织的炎症反应、氧化应激。

Abstract

OBJECTIVE

To study the effects of leonurine on pancreatic injury in rats with severe acute pancreatitis （SAP）， and to explore its mechanism based on the high-mobility group box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signaling pathway.

METHODS

SAP rat model was constructed by injecting 5% sodium taurocholate into the bile duct of the pancreas. Model rats were randomly divided into model group， low dose leonurine group （8 mg/kg）， high dose leonurine group （16 mg/kg）， HMGB1 overexpression group （8 μg/kg）， and high dose leonurine+HMGB1 overexpression group （16 mg/kg+8 μg/kg）， with 14 rats in each group. Another 14 rats were selected as the sham operation group. Rats in each group were injected with corresponding drugs or normal saline via abdominal cavity or tail vein once a day for 5 consecutive days. After the last administration， the levels of serum amylase （AMS） and lipase （LPS） were detected； the pathological injury of pancreatic tissue was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， malondialdehyde （MDA） and superoxide dismutase （SOD）， mRNA and protein expressions of HMGB1 and RAGE in pancreatic tissues were detected.

RESULTS

Compared with model group， the structure of pancreatic tissue in rats gradually recovered in low and high dose leonurine groups； inflammatory cell infiltration gradually decreased； the pathological injury score and the levels of AMS， LPS， TNF-α， IL-6， MDA， the mRNA and protein expressions of HMGB1 and RAGE were significantly decreased， while the SOD levels were significantly increased （

＜0.05）. The high dose leonurine group showed more significant improvement （

＜0.05）； the pathological damage of pancreatic tissue in the HMGB1 overexpression group worsened， and except for a decrease in SOD levels， all other quantitative indicators increased significantly （

＜0.05）. Overexpression of HMGB1 could reduce the improvement effect of high dose leonurine on the above indexes in SAP rats （

＜0.05）.

CONCLUSIONS

Leonurine may alleviate pancreatic injury， inflammation and oxidative stress in pancreatic tissue of rats with SAP by inhibiting the HMGB1/RAGE signaling pathway.

关键词

益母草碱重症急性胰腺炎高迁移率族蛋白1晚期糖基化终产物受体胰腺损伤

Keywords

severe acute pancreatitisHMGB1RAGEpancreatic injury

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