吲哚美辛通过恢复自噬流减轻雨蛙素诱导的小鼠急性胰腺炎  

Indomethacin alleviates cerulein-induced acute pancreatitis in mice by restoring autophagy flux

作　　者：楼立君 李人龙 李雁 李静 康晓宇 王向平 潘阳林 LOU Lijun;LI Renlong;LI Yan;LI Jing;KANG Xiaoyu;WANG Xiangping;PAN Yanglin(State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]国家消化系统疾病临床医学研究中心,消化系肿瘤整合防治全国重点实验室,空军军医大学西京消化病医院,陕西西安710032

出　　处：《空军军医大学学报》2024年第3期263-269,共7页Journal of Air Force Medical University

基　　金：国家自然科学基金(81970557)。

摘　　要：目的探究吲哚美辛对雨蛙素诱导的小鼠急性胰腺炎(AP)的影响。方法将28只C57BL/6小鼠随机分为对照组、吲哚美辛组、雨蛙素组、雨蛙素+吲哚美辛组,通过雨蛙素(50μg/kg)腹腔注射法建立小鼠AP模型,雨蛙素+吲哚美辛组在第一次雨蛙素注射前6 h和0.5 h给予2次吲哚美辛(8 mg/kg)腹腔注射。HE染色观察小鼠胰腺组织形态学改变并进行组织病理学评分;检测血清淀粉酶与脂肪酶水平;免疫组化检测髓过氧化物酶阳性(MPO+)细胞数;qPCR检测炎症因子mRNA表达;电镜检测各组自噬空泡数量;Western blotting检测自噬相关蛋白LC3-Ⅱ与P62的表达。结果与对照组相比,雨蛙素组组织病理学评分增加(P<0.05);血清淀粉酶与脂肪酶明显升高(P<0.05);MPO+细胞数及炎症因子mRNA的表达水平升高(P<0.05);自噬空泡增多,LC3-Ⅱ与P62蛋白表达升高(P<0.05)。与雨蛙素组相比,雨蛙素+吲哚美辛组胰腺组织炎症样变减轻,组织病理学评分降低(P<0.05);血清淀粉酶与脂肪酶水平明显降低(P<0.05);MPO+细胞数及炎症因子mRNA的表达水平降低(P<0.05);异常堆积的自噬空泡减少,LC3-Ⅱ与P62蛋白的表达也下降(P<0.05)。结论本研究发现吲哚美辛可以减轻雨蛙素诱导的小鼠胰腺组织损伤并改善AP时受损的自噬流,提示吲哚美辛可能通过恢复受损的自噬流发挥其对小鼠AP的保护作用。Objective To investigate the effect of indomethacin on cerulein-induced acute pancreatitis(AP)in mice.Methods Twenty-eight C57BL/6 mice were randomly divided into control group,indomethacin group,cerulein group,and cerulein+indomethacin group.A mouse AP model was established by intraperitoneal injection of cerulein(50μg/kg).Cerulein+indomethacin group was given two intraperitoneal injections of indomethacin(8 mg/kg)at 6 h and 0.5 h before the first injection of cerulein.The histopathological changes of pancreas were observed by HE staining and histopathological scores were performed.Serum amylase and lipase levels were detected.The number of MPO+cells was detected by immunohistochemistry,the mRNA expression of inflammatory factors was detected by qPCR,the number of autophagic vacuoles in each group was detected by electron microscopy,and the expression of autophagy-related proteins LC3-Ⅱand P62 was detected by Western blotting.Results Compared with the control group,the cerulein group showed an increase in histopathological scores(P<0.05),serum amylase and lipase levels(P<0.05),number of MPO+cells and mRNA expression levels of inflammatory factors(P<0.05),number of autophagic vacuoles,and expression of LC3-Ⅱand P62 proteins(P<0.05).Compared with the cerulein group,the cerulein+indomethacin group showed a decrease in inflammatory changes of pancreatic tissue,histopathological scores(P<0.05),serum amylase and lipase levels(P<0.05),number of MPO+cells and mRNA expression levels of inflammatory factors(P<0.05),abnormal accumulation of autophagic vacuoles,and expression of LC3-Ⅱand P62 proteins(P<0.05).Conclusion This study finds that indomethacin can alleviate cerulein-induced pancreatic tissue damage and improve impaired autophagic flux in mice,suggesting that indomethacin may exert its protective effect on AP in mice by restoring the impaired autophagic flux.

关 键 词：急性胰腺炎 吲哚美辛 雨蛙素 自噬 

分 类 号：R576[医药卫生—消化系统]