佐替平通过NF-κB通路改善重症急性胰腺炎大鼠肠损伤的机制研究
投稿时间:2025-01-19  修订日期:2025-02-28  点此下载全文
引用本文:刘贻晶,林钰洁,张玲,马向丽,刘世显,曹成龙,李培武.佐替平通过NF-κB通路改善重症急性胰腺炎大鼠肠损伤的机制研究[J].医学研究杂志,2025,54(7):60-65
DOI: 10.11969/j.issn.1673-548X.2025.07.012
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作者单位
刘贻晶 兰州大学第二医院(第二临床医学院)急救中心,730000 
林钰洁 兰州大学第二医院(第二临床医学院)急救中心,730000 
张玲 兰州大学第二医院(第二临床医学院)急救中心,730000 
马向丽 兰州大学第二医院(第二临床医学院)急救中心,730000 
刘世显 兰州大学第二医院(第二临床医学院)急救中心,730000 
曹成龙 兰州大学第二医院(第二临床医学院)急救中心,730000 
李培武 兰州大学第二医院(第二临床医学院)急救中心,730000 
基金项目:国家自然科学基金资助项目(82260135)
中文摘要:目的 研究佐替平作用于p65/p-p65介导的核因子-κB(nuclear factor-κB,NF-κB)通路对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)相关肠损伤的影响。方法 将18只SD雄性大鼠随机分为假手术组(Sham组)、SAP组和佐替平组。采用3%戊巴比妥钠腹腔注射诱导麻醉后,Sham组大鼠开腹并行胰胆管内逆行注射0.9%氯化钠溶液(1ml/kg);SAP组和佐替平组通过胰胆管内逆行注射3.5%牛黄胆酸钠(1ml/kg)造模;佐替平组在造模前2h和造模后2h分别腹腔注射佐替平溶液(3mg/kg)。于术后24h采集样本。使用生化试剂盒和酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测血清淀粉酶、相关炎性细胞因子水平及内毒素含量;Western blot法检测相关蛋白水平;光学显微镜观察肠组织病理变化;免疫荧光检测p65、p-p65在肠组织中的分布。结果 肠组织的病理损伤程度在佐替平的干预下呈下降趋势,且佐替平组的淀粉酶、内毒素及相关炎性细胞因子水平较SAP组降低,差异有统计学意义(P<0.05);同时Western blot法检测结果显示,p65向p-p65的转化也被抑制。结论佐替平能够通过抑制NF-κB通路,改善大鼠SAP的肠损伤。
中文关键词:佐替平 急性胰腺炎 急性胰腺炎相关肠损伤 p-p65 p65
 
Zotepine Improves Intestinal Injury in Rats with Severe Acute Pancreatitis Through NF-κB Pathway.
Abstract:Objective To investigate the effects of Zotepine on intestinal damage associated with severe acute pancretitis(SAP) in rats treated with p65/ p-p65-mediated NF-κB signaling pathway. Methods Eighteen SD male rats were randomly divided into Sham group, SAP group and Zotepine group. After intraperitoneal injection of 3% pentobarbital sodium to induce anesthesia, the rats in Sham group were given retrograde injection of 1ml/kg normal saline into the pancreatic bile duct after laparotomy. SAP group and Zotepine group were molded by retrograde injection of 3.5% sodium taurine cholate (1ml/kg) into the bile duct of the pancreas, and zotepine group was injected intraperitoneally with zotepine solution (3mg/kg) two hours before and after modeling, and serum and related tissue samples were collected 24hours after surgery. Biochemical kit and enzyme-linked immunosorbent assay (ELISA) were used to detect serum amylase, related inflammatory factors and endotoxin content. The levels of related proteins were detected by Western blot. The pathological changes of intestinal tissue were observed by optical microscope, and the distribution of p65 and p-p65 in intestinal tissue was detected by immunofluorescence. Results The pathological damage degree of intestinal tissue showed a decreasing trend under the intervention of zotepine. The levels of amylase, endotoxin and related inflammatory factors in the Zotepine group were significantly reduced compared with those in the SAP group(P<0.05). Meanwhile, Western blot results indicated that the conversion of p65 to p-p65 was also inhibited. Conclusion Zotepine can improve intestinal injury induced by severe acute pancreatitis in rats by inhibiting NF-κB pathway.
keywords:Zotepine  Acute pancreatitis  Acute pancreatitis associated intestinal injury  p-p65  p65
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