肿瘤坏死因子α诱导蛋白8样分子1在小鼠急性肝损伤中的作用及机制  

Role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1 in acute liver injury in mice

作　　者：常勇生 田雪钦 赵雨欣 宋苗苗 王涵 娄运伟 常廷民[1] CHANG Yongsheng;TIAN Xueqin;ZHAO Yuxin;SONG Miaomiao;WANG Han;LOU Yunwei;CHANG Tingmin(Department of Gastroenterology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Henan Key Laboratory of Immunology and Targeted Drugs,Xinxiang 453003,Henan Province,China;Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine,Xinxiang 453003,Henan Province,China)

机构地区：[1]新乡医学院第一附属医院消化内科,河南卫辉453100 [2]河南省免疫与靶向药物重点实验室,河南新乡453003 [3]河南省分子诊断与医学检验技术协同创新中心,河南新乡453003

出　　处：《新乡医学院学报》2024年第8期712-717,共6页Journal of Xinxiang Medical University

基　　金：国家自然科学基金资助项目(编号:81971491);河南省自然科学基金项目(编号:222300420066)。

摘　　要：目的探讨肿瘤坏死因子α诱导蛋白8样分子1(TNFAIP8L1)在小鼠急性肝损伤中的作用及机制。方法选择C57BL/6J雄性野生型(WT)小鼠和C57BL/6J雌性TNFAIP8L1^(+/-)小鼠杂交繁殖的第2代TNFAIP8L1^(+/-)小鼠和WT小鼠,进一步自交繁殖出第3代雄性TNFAIP8L1^(-/-)小鼠和第3代WT雄性小鼠。分别取5只正常第3代雄性WT小鼠和5只正常第3代雄性TNFAIP8L1^(-/-)小鼠,检测比较2种正常小鼠的血清丙氨酸氨基转移酶(ALT)水平,苏木精-伊红(HE)染色观察2种正常小鼠肝组织中炎症细胞浸润及细胞坏死情况,采用流式细胞术检测2种正常小鼠肝组织髓系细胞亚群中性粒细胞(Neu)、嗜酸性粒细胞(EOS)、树突状细胞(DC)、骨髓来源的巨噬细胞(BMDMs)、骨髓来源的单核细胞(BMNCs)所占百分比。另取5只第3代雄性WT小鼠和4只第3代雄性TNFAIP8L1^(-/-)小鼠,采用脂多糖(LPS)/D-半乳糖胺(D-Gal)诱导制备急性肝损伤小鼠模型,24 h后采取上述方法检测比较2种急性肝损伤小鼠血清ALT水平,观察2种急性肝损伤小鼠肝组织中炎症细胞浸润及细胞坏死情况,并检测2种急性肝损伤小鼠肝组织髓系细胞亚群Neu、EOS、DC、BMDMs、BMNCs所占百分比。结果正常WT小鼠和TNFAIP8L1^(-/-)组小鼠肝组织中髓系细胞亚群Neu、EOS、DC、BMDMs、BMNCs百分比及血清ALT水平比较差异无统计学意义(P>0.05)。正常WT小鼠和TNFAIP8L1^(-/-)小鼠的肝组织HE染色结果均显示肝小叶结构完整清晰,肝细胞形态正常、排列整齐,无明显炎症细胞浸润及细胞坏死。急性肝损伤24 h后,TNFAIP8L1^(-/-)小鼠肝组织髓系细胞亚群中Neu、BMNCs百分比及血清ALT水平显著高于WT小鼠(P<0.05);2组小鼠肝组织髓系细胞亚群EOS、DC、BMDMs百分比比较差异无统计学意义(P>0.05)。急性肝损伤WT小鼠肝组织中肝小叶结构模糊,肝细胞肿胀、散在空泡样脂肪变性,有少量炎症细胞浸润。急性肝损伤TNFAIP8L1^(-/-)小鼠肝组织中肝小叶结Objective To investigate the role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1(TNFAIP8L1)in acute liver injury in mice.Methods The second generation of C57BL/6J male wild-type(WT)mice and the C57BL/6J female TNFAIP8L1^(+/-)mice and WT mice were selected to further self-breed the third generation of male TNFAIP8L1^(-/-)mice and the third generation of WT male mice.Five normal third-generation male WT mice and five normal third-generation male TNFAIP8L1^(-/-)mice were selected.The serum alanine aminotransferase(ALT)levels of the two types of normal mice were measured and compared.The infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of normal mice were observed after hematoxylin&eosin(HE)staining.Flow cytometry was used to detect the percentages of neutrophils(Neu),eosinophils(EOS),dendritic cells(DC),bone marrow-derived macrophages(BMDMs),and bone marrow-derived mononuclear cell(BMNCs)in the liver myeloid cell subsets of the two types of normal mice.Another 5 third-generation male WT mice and 4 third-generation male TNFAIP8L1^(-/-)mice were selected to induce acute liver injury mouse models using lipopolysaccharide(LPS)/D-galactosamine(D-Gal).After 24 hours,the serum ALT levels of the two types of acute liver injury mice were detected and compared,the infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of acute liver injury mice were observed,and the percentages of Neu,EOS,DC,BMDMs and BMNCs in the liver myeloid cell subsets of the two types of acute liver injury mice were measured by using the above methods.Results There was no significant difference in the percentages of Neu,EOS,DC,BMDMs and BMNCs,and serum ALT levels in the livermyeloid cell subsets of normal WT mice and TNFAIP8L1^(-/-)mice(P>0.05).HE staining results of liver tissues in normal WT mice and TNFAIP8L1^(-/-)mice showed that hepatic lobules were structurally complete and clear,hepatocytes were morphologically normal and arr

关 键 词：肿瘤坏死因子α诱导蛋白8样分子1 急性肝损伤 中性粒细胞 单核细胞 

分 类 号：R575[医药卫生—消化系统]