4-辛基衣康酸加重小鼠肠缺血/再灌注诱导的肠损伤及远端器官损伤  

4⁃octyl itaconate aggravates intestinal ischemia/reperfusion⁃induced intestinal injury and remote organ injury in mice

作　　者：吴熙成 孙弋力 宁海燕 张雪 张力 杨永强 WU Xi-cheng;SUN Yi-li;NING Hai-yan;ZHANG Xue;ZHANG Li;YANG Yong-qiang(Department of Pathophysiology,College of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China;Hospital of Chongqing University of Arts and Sciences,Chongqing 402160,China)

机构地区：[1]重庆医科大学基础医学院病理生理学教研室,重庆400016 [2]重庆文理学院校医院,重庆402160

出　　处：《毒理学杂志》2023年第4期344-349,共6页Journal of Toxicology

摘　　要：目的探讨4-辛基衣康酸(4⁃octyl itaconate,4⁃OI)在小鼠肠缺血/再灌注(ischemia reperfusion,I/R)损伤中的作用。方法将32只雄性C57BL/6小鼠随机分为4组(n=8):假手术组、4⁃OI对照组、肠I/R组和4⁃OI处理组。采用夹闭肠系膜上动脉1.5 h再灌注3 h的方法复制肠I/R损伤模型。利用相关试剂盒测定小鼠血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性、小肠组织丙二醛(MDA)水平及含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase⁃3)活性。采用苏木精-伊红(HE)染色观察小肠和肺的组织病理学异常。采用酶联免疫吸附法检测小鼠血清白细胞介素-6(IL⁃6)和肺组织髓过氧化物酶(MPO)的水平。结果4⁃OI处理加重肠I/R诱导的小肠和肺组织病理学异常,升高小肠组织内MDA含量(F=2.730,P<0.05)及Caspase⁃3的活性(F=2.645,P<0.01),上调肠I/R小鼠血清中IL⁃6(F=3.087,P<0.01)、AST(F=1.303,P<0.01)、ALT(F=2.661,P<0.01)水平和肺内MPO(F=2.897,P<0.01)的含量。结论4⁃OI可加重肠I/R诱导的小肠及远端器官的损伤。Objective To investigate the effect of 4⁃octyl itaconate(4⁃OI)on intestinal ischemia/reperfusion(I/R)injury in mice.Methods Thirty⁃two C57BL/6 male mice were randomly divided into 4 groups(n=8):sham operation group,4⁃OI group,intestinal I/R group,4⁃OI treatment group.Intestinal I/R injury was induced by clipping the superior mesenteric artery for 1.5 h and following by a reperfusion for 3 h.The detecting kits were employed to determine the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,the content of malondialdehyde(MDA)and the activity of cysteinyl aspartate⁃specific proteinase⁃3(Caspase⁃3)in small intestinal.Hematoxylin and eosin staining was used to observe the histopathological abnormalities of small intestine and lung.Enzyme Linked immunosorbent assay kits were used to detect the level of interleukin⁃6(IL⁃6)in serum and the content of myeloperoxidase(MPO)in lung tissue.Results 4⁃OI aggravated the pathological abnormalities of small intestine and lung,increased the content of MDA(F=2.730,P<0.05)and the activity of Caspase⁃3(F=2.645,P<0.01)in small intestine.4⁃OI also up⁃regulated the serum levels of IL⁃6(F=3.087,P<0.01),AST(F=1.303,P<0.01)and ALT(F=2.661,P<0.01)and the content of pulmonary MPO(F=2.897,P<0.01)in mice with intestinal I/R injury.Conclusion 4⁃OI aggravated intestinal I/R induced small intestine injury and distal organ damage.

关 键 词：4-辛基衣康酸 肠缺血-再灌注损伤 炎症 氧化应激 凋亡 

分 类 号：R99[医药卫生—毒理学] R114[医药卫生—药学]