急性肝功能衰竭大鼠肝组织内巨噬细胞形态变化特点

摘要

目的：探讨肝组织内巨噬细胞在急性肝功能衰竭（acute liver failure，ALF）大鼠模型中的形态变化及其在肝脏炎性损伤中的意义。方法 Wistar 大鼠分为两组：实验对照组6只，模型组24只。通过腹腔注射 D-氨基半乳糖（D-GalN）及脂多糖（LPS）建立大鼠急性肝功能衰竭模型，动态观察各时间点（4、8、16、24 h）大鼠肝组织的病理变化以及 ALT、AST、TBil 和 TNF-α的含量变化，通过透射电镜观察各时间点大鼠肝组织中巨噬细胞的形态变化。结果D-GalN/LPS联合注射成功诱导大鼠急性肝功能衰竭模型，表现为建立模型后 ALT、AST 及 TBil 水平显著上升，于造模后24 h 表达最高（犘＜0．01），病理变化符合急性肝功能衰竭的病理特点。以细胞体积增大、形状不规则、胞质伸出较多微绒毛和伪足者为激活的巨噬细胞判断标准。建立模型后，在同样放大倍数下，肝组织中巨噬细胞形态发生变化，以8 h 模型组的大鼠肝组织中巨噬细胞的形态变化最为明显，随着炎性反应的进一步发展，其形态变化反而减弱。与此同时，TNF-α建立模型后其含量逐渐升高，以8 h 模型组的大鼠血清内含量最高，此后逐渐下降。结论肝组织中巨噬细胞参与急性肝功能衰竭的病理生理过程，其在急性肝功能衰竭的初始阶段及促进炎性反应发展中发挥了重要的作用。%Objective To investigate the morphological changes and the role of macrophages in rats with acute liver failure (ALF).Methods Wistar rats were divided into two groups.Model group (24 rats)was give by D-GalN and LPS, whose dosage were according to their weight,and control group (6 rats)was given by 0.9% NaCl (2ml)by intraperitoneal injection.Levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total billirubin (TBil)and TNF-α,and morphological changes of macrophages by transmission electron microscope of each rat were dynamically observed at 4,8,16 and 24 hours after modeling.Results Animal model of ALF could be established by D-GalN combined with LPS in rats successfully.Levels of ALT,AST and TBil were increased and peaked at 24h after modeling,pathological changes in accordance with the pathological characteristics of ALF.The activation of macrophages has evalution criteria,including the size of cells increased,irregular shape and many microvilli and pseudopods were protruded in cytoplasm.On the same condi-tion of magnification,morphological changes of macrophages in liver tissue were observed.The morphological changes of macrophages were most obvious at 8 hours after modeling,and with the further development of inflammation,the extent of morphological changes became weaker.Level of TNF-α from serum was gradually increased with the development of inflammation and peaked at 8h after injection with D-GalN/LPS(犘<0.01 ),and then decreased.Conclusion By transmission electron microscope,it is observed that macrophages participate in the pathological processes of ALF and play an important role in both initial stage and inflammation-promoting stage of ALF.