[1]贺晓林,孟唤男,赵航,等.EMO联合BMSCs对重症急性胰腺炎大鼠的保护作用及机制实验研究[J].陕西医学杂志,2025,54(9):1183-1188.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.005]
　HE Xiaolin,MENG Huannan,ZHAO Hang,et al.Protective effect and mechanism of EMO with BMSCs on severe acute pancreatitis rats[J].,2025,54(9):1183-1188.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.005]
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EMO联合BMSCs对重症急性胰腺炎大鼠的保护作用及机制实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年9期
页码:
1183-1188
栏目:
基础研究
出版日期:
2025-09-05

文章信息/Info

Title:
Protective effect and mechanism of EMO with BMSCs on severe acute pancreatitis rats
作者:
贺晓林1; 2; 孟唤男2; 赵航2; 李亚希1
（1.上海中医药大学中西医结合临床专业，上海 201203；2.上海中医药大学附属市中医医院消化内科，上海 201203）
Author(s):
HE Xiaolin1; 2; MENG Huannan2; ZHAO Hang2; LI Yaxi1
(1.Clinical Practice of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;2.Department of Gastroenterology,Affiliated Traditional Chinese Medicine Hospital of Shanghai University of Chinese Medicine,Shanghai 201203,China)
关键词:
重症急性胰腺炎; 大黄素; 转化生长因子β1; Smad; 细胞外信号调节蛋白激酶; 骨髓间充质干细胞
Keywords:
Severe acute pancreatitis; Emodin; Transforming growth factor-β1; Smad; Extracellular regulated protein kinase; Bone marrow mesenchymal stem cells
分类号:
R 285
DOI:
DOI:10.3969/j.issn.1000-7377.2025.09.005
文献标志码:
A
摘要:
目的：基于转化生长因子β1（TGF-β1）/Smad/细胞外信号调节蛋白激酶（ERK）信号通路探究大黄素（EMO）联合骨髓间充质干细胞（BMSCs）对重症急性胰腺炎（SAP）大鼠的保护作用及机制。方法：构建SAP大鼠模型，将建模成功的大鼠分为SAP组、EMO组（灌胃60 mg/kg EMO）、BMSCs组（尾静脉注射1×106个BMSCs）、EMO＋BMSCs组（灌胃60 mg/kg EMO＋尾静脉注射1×106个BMSCs）、EMO＋BMSCs＋SRI-011381组（灌胃60 mg/kg EMO＋尾静脉注射1×106个BMSCs＋腹腔注射7 mg/kg TGF-β1/Smad/ERK信号通路激活剂SRI-011381），每组10只。另取10只正常大鼠为Ctrl组，Ctrl组与SAP组给予等量0.9%氯化钠溶液，分别于造模后12 h后给药，1次/d，共14 d。HE染色观察大鼠胰腺组织病理变化并进行病理评分；商用试剂盒检测大鼠血清淀粉酶（AMS）、脂多糖（LPS）水平；酶联免疫吸附试验（ELISA）检测大鼠胰腺组织白细胞介素6（IL-6）、IL-1β水平；硫代巴比妥酸法检测大鼠胰腺组织中丙二醛（MDA）含量、羟胺法检测超氧化物歧化酶（SOD）活性；Western blot检测大鼠胰腺组织TGF-β1/Smad/ERK信号通路相关蛋白表达。结果：SAP组大鼠较Ctrl组胰腺组织腺体结构紊乱，伴大量炎症细胞浸润；EMO组、BMSCs组、EMO＋BMSCs组大鼠较SAP组胰腺组织病理变化不同程度减轻，其中EMO＋BMSCs组改善更为明显；EMO＋BMSCs＋SRI-011381组大鼠较EMO＋BMSCs组胰腺组织损伤加重。SAP组大鼠Schmidt评分，血清AMS、LPS水平，胰腺组织IL-6、IL-1β、MDA水平以及TGF-β1、p-Smad2/3/Smad2/3、p-ERK1/2/ERK1/2蛋白表达较Ctrl组高，SOD水平较Ctrl组低（均P＜0.05）；EMO组、BMSCs组、EMO＋BMSCs组大鼠Schmidt评分，血清AMS、LPS水平，胰腺组织IL-6、IL-1β、MDA水平以及TGF-β1、p-Smad2/3/Smad2/3、p-ERK1/2/ERK1/2蛋白表达较SAP组低，SOD水平较SAP组高，且EMO＋BMSCs组以上指标变化更加显著（均P＜0.05）；EMO＋BMSCs＋SRI-011381组大鼠Schmidt评分，血清AMS、LPS水平，胰腺组织IL-6、IL-1β、MDA水平以及TGF-β1、p-Smad2/3/Smad2/3、p-ERK1/2/ERK1/2蛋白表达较EMO＋BMSCs组高，SOD水平较EMO＋BMSCs组低（均P＜0.05）。结论：EMO联合BMSCs可通过抑制TGF-β1/Smad/ERK信号通路减轻SAP大鼠胰腺损伤。
Abstract:
Objective:To discuss the protective effect and mechanism of emodin (EMO) combined with bone marrow mesenchymal stem cells (BMSCs) on severe acute pancreatitis (SAP) rats based on the transforming growth factor-β1 (TGF-β1)/Smad/extracellular signal-regulated kinase (ERK) signaling pathway.Methods：A SAP rat model was constructed,and successfully modeled rats were assigned into SAP group,EMO group (orally administered 60 mg/kg EMO),BMSCs group (tail vein injection of 1×106 BMSCs),EMO+BMSCs group (orally administered 60 mg/kg EMO+tail vein injection of 1×106 BMSCs),and EMO+BMSCs+SRI-011381 group (orally administered 60 mg/kg EMO+tail vein injection of 1×106 BMSCs+intraperitoneal injection of 7 mg/kg TGF-β1/Smad/ERK signaling pathway activator SRI-011381),each with 10 rats.Another 10 normal rats were served as the Ctrl group.The Ctrl group and SAP group were given equal amounts of 0.9% sodium chloride solution,which was administered 12 hours after modeling,once a day for a total of 14 days.HE staining was used to observe pathological changes in rat pancreatic tissue,and the pathological scoring was performed.Commercial test kits were used to measure AMS and LPS in serum.ELISA was used to measure the IL-6 and IL-1β in pancreatic tissue.The thiobarbituric acid method was used to measure the MDA content in rat pancreatic tissue.The hydroxylamine method was used to measure SOD activity.Western blot was used to detect the TGF-β1/Smad/ERK signaling pathway proteins in rat pancreatic tissue.Results:The pancreatic tissue glandular structure of rats in SAP group was more disordered than that of Ctrl group,accompanied by a large amount of inflammatory cell infiltration.The pathological changes in pancreatic tissue of rats in the EMO group,BMSCs group,and EMO+BMSCs group were alleviated to varying degrees compared to the SAP group,with the EMO+BMSCs group showing more prominent improvement.The pancreatic tissue damage in the EMO+BMSCs+SRI-011381 group was more severe than that in the EMO+BMSCs group.The SAP group had higher Schmidt score,serum AMS and LPS,pancreatic tissue IL-6,IL-1β,MDA levels,and TGF-β1,p-Smad2/3/Smad2/3,p-ERK1/2/ERK1/2 proteins,and lower SOD than the Ctrl group (all P<0.05).The EMO group,BMSCs group,and EMO+BMSCs group had lower Schmidt score,serum AMS and LPS,pancreatic tissue IL-6,IL-1β,MDA levels,and TGF-β1,p-Smad2/3/Smad2/3,p-ERK1/2/ERK1/2 proteins,and higher SOD than the SAP group,and the EMO+BMSCs group showed more prominent changes in these indicators (all P<0.05).The EMO+BMSCs+SRI-011381 group had higher Schmidt score,serum AMS and LPS,pancreatic tissue IL-6,IL-1β,MDA levels,and TGF-β1,p-Smad2/3/Smad2/3,p-ERK1/2/ERK1/2 proteins,and lower SOD than the EMO+BMSCs group (all P<0.05).Conclusion:EMO combined with BMSCs can alleviate pancreatic injury in SAP rats by inhibiting TGF-β1/Smad/ERK signaling pathway.

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备注/Memo

备注/Memo:
医学免疫学国家重点实验室课题（2024Q0011）
更新日期/Last Update: 2025-09-04