游离血红素直接致肝细胞损伤的研究  

The Study on Hepatocyte Injury Directly Caused by Free Heme

作　　者：吴晓双 安宁 陈要臻 王雅芬 刘志新 胡兴斌 WU Xiaoshuang;AN Ning;CHEN Yaozhen(Department of Transfusion Medicine,the First Affiliated Hospital of Air Force Military Medical University,Shaanxi Province,Xi'an 710032)

机构地区：[1]空军军医大学第一附属医院输血科,陕西西安710032

出　　处：《临床输血与检验》2023年第4期444-449,共6页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：空军军医大学发展基金(No.2022XC042)资助。

摘　　要：目的研究溶血发生时游离血红素是否可以直接损伤肝细胞而致肝细胞功能异常。方法建立溶血性输血反应小鼠模型,检测谷丙转氨酶(ALT)、谷草转氨酶(AST)等生化指标分析肝功能水平;在体外,分别用不同浓度的红细胞裂解液上清和血红素刺激人正常肝细胞LO2细胞,通过检测ALT、AST等生化指标分析肝功能,通过流式细胞术检测细胞死亡情况,通过免疫荧光观察细胞形态与骨架结构。结果在溶血性输血反应小鼠模型上可明显观察到肝脏功能异常;体外实验证实,随着游离血红素浓度升高,LO2细胞活力下降、细胞死亡比例增加,ALT、AST等生化指标显著性增高,肝细胞骨架结构被明显破坏。结论游离血红素可以直接破坏肝细胞骨架结构、抑制细胞活力,导致肝细胞功能异常,并且损伤程度与游离血红素浓度成正相关性。Objective To investigate whether free heme released in hemolysis could directly damage hepatocytes and disrupt liver function.Methods The mice model of hemolytic transfusion reaction was established,and ALT,AST and other biochemical indexes were detected to analyze the liver function.In vitro,the LO2 cells were stimulated with different concentrations of lysed supernatant of red blood cells and heme respectively.Then the levels of ALT and AST were detected to analyze the liver function.Cell viability was observed by flow cytometry,and cell morphology and skeleton structure were observed by immunofluorescence.Results Abnormal liver function was observed on the mice model of hemolytic transfusion reaction.The results of in vitro experiments showed that LO2 cell viability decreased and the proportion of dead cells increased along with the incremental concentration of free heme.The biochemical indexes such as ALT and AST were aggravated significantly.And free heme could directly destroy the cytoskeleton of LO2 cells.Conclusion Free heme can directly destroy the cell structure of hepatocytes,inhibit cell vitality,induce cell death and abnormal liver function.The degree of damage is positively correlated with the concentration of free heme.

关 键 词：溶血 血红素 人肝脏正常细胞LO2 肝脏功能损伤 

分 类 号：R457[医药卫生—治疗学]