野百合碱致肝窦阻塞综合征与中性粒细胞胞外诱捕网的关联性研究  

Association between hepatic sinusoidal obstruction syndrome induced by monocrotaline and neutrophil extracellular traps

作　　者：李玥[1] 张爽 孙鑫[1] 刘成海[1] 裘福荣[1] LI Yue;ZHANG Shuang;SUN Xin;LIU Chenghai;QIU Furong(Shuguang Hospital Affiliated to Shanghai University of Tradi­tional Chinese Medicine,Shanghai 201210,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201210

出　　处：《中国药物警戒》2023年第2期121-126,共6页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81874364、82274305);上海市中医重点实验室资助项目(20DZ2272200);上海市科学技术委员会科技计划项目(20Z21900100)。

摘　　要：目的 研究野百合碱诱导的肝窦阻塞综合征(HSOS)与中性粒细胞胞外诱捕网(NET)的关联性。方法 根据体重将SD大鼠随机分为正常组和HSOS模型组,每组5只。正常组灌胃生理盐水,模型组1次灌胃野百合碱(90 mg·kg^(-1))造模。48h后收集各组大鼠血浆及肝组织,测定肝脏病理改变、谷丙转氨酶(ALT)和碱性磷酸酶(ALP)活力、肝脏髓过氧化物酶(MPO)水平、瓜氨酸化组蛋白3(Cit H3)蛋白表达、NET结构免疫荧光染色及NETs相关基因表达。结果 经野百合碱造模后,模型组大鼠肝组织肿大,表面明显淤血。HE染色观察到血管壁肿胀、窦周红细胞及炎性细胞浸润、肝实质细胞坏死。与正常对照组比较,模型组大鼠血浆ALT和ALP水平升高明显(P<0.01),肝脏MPO活力及Cit H3蛋白表达显著升高(P<0.01),荧光显微镜下可观察到NET的网状结构。此外,诱导中性粒细胞募集及NET生成的趋化因子受体2(CXCR2)和Toll样受体4(TLR4)的mRNA水平均显著升高(P<0.01)。结论 NET可能在野百合碱诱导的HSOS发病过程中发挥作用。Objective To investigate the association between neutrophil extracellular traps(NET) and hepatic sinusoidal obstruction syndrome(HSOS) induced by monocrotaline(MCT).Methods Ten Sprague-Dawley(SD) rats were randomly divided into the normal group and HSOS model group based on body weight,with five in each.The normal group was gavaged with saline while the model group received a single gavage of MCT(90 mg·kg^(-1)).Forty-eight hours after MCT administration,blood and liver samples were collected.The effects of MCT on histological changes of the liver,alanine aminotransferase and alkaline phosphatase levels,hepatic myeloperoxidase activity,protein expression of citrullinated histone H3(Cit H3),immunofluorescence staining of NET structure as well as expressions of NET associated genes were investigated.Results In the model group,macroscopic and histological findings revealed liver congestion,sinusoidal alteration,perisinusoidal infiltration of red cells and inflammatory cells,and multifocal hepatocellular necrosis.Furthermore,plasma ALT and ALP levels were significantly increased compared with the normal group(P<0.01).Administration of MCT to rats resulted in a significant elevation of hepatic MPO activity and Cit H3 expression.It NET formation was also observed in the liver lobes in MCT-treated rats.Additionally,the mRNA levels of C-X-C motif chemokine receptor 2(CXCR2),and toll-like receptor 4(TLR4) were significantly increased in the MCT group(P<0.01).Conclusion NET may be involved in the mechanism responsible for MCT-induced HSOS.

关 键 词：中性粒细胞胞外诱捕网 肝窦阻塞综合征 野百合碱 大鼠 

分 类 号：R979.1[医药卫生—药品] R994[医药卫生—药学]