氟美松对急性肝损伤大鼠肝细胞Fas/Fas配体表达和细胞凋亡的影响

目的 :观察内毒素急性肝损伤后肝细胞凋亡和Fas/Fas配体 (FasL)表达的变化 ,以及氟美松对其影响 ,探讨急性肝损伤早期作用机制 .方法 :采用免疫组化和原位杂交技术检测各时相点肝细胞Fas/FasL蛋白和mRNA的表达 ;应用原位末端标记技术对各时相点肝细胞凋亡进行检测 .结果 :内毒素急性肝损伤各时相点大鼠肝细胞Fas/FasL蛋白和mR NA的表达较对照组明显上调 (P <0 .0 5 ) ,且与肝细胞凋亡的增加相一致 ;氟美松可明显减轻炎症反应 ,抑制脂多糖 (LPS)诱导的肝细胞凋亡 ,并使肝细胞Fas/FasL蛋白和mRNA的表达明显下调 (P <0 .0 5 ) .结论 :肝细胞凋亡和Fas/FasL系统活化可能参与内毒素急性肝损伤早期的发病机制 ,而且加重早期肝损伤 ;氟美松可抑制Fas/FasL系统活化 ,阻断和调控凋亡 ,从而减轻肝组织损伤

Effects of dexamethasone on Fas/Fas ligand expression and apoptosis of hepatocytes in rats with LPS-induced acute liver injury

AIM: To investigate the changes of expression of hepatocytes apoptosis and Fas/Fas ligand (FasL) in lipopolysaccharide (LPS) induced acute liver injury in rats and the effects of treatment by dexamethasone and to evaluate the potential role and mechanism in the pathogenesis of acute liver injury. METHODS: Expression of Fas/FasL protein and mRNA was detected using immunohistochemistry and in situ hybridization, respectively. Apoptosis was determined by terminal UTP nick end labelling (TUNEL) in rats during every phase of acute liver injury. RESULTS: Expression of Fas/FasL protein and mRNA was upregulated and correlated with the increased apoptosis in hepatocytes of rats with lipopolysaccharide (LPS) induced acute liver injury ( P <0.05). The administration of dexamethasone suppressed apoptosis as well as expression of Fas/FasL protein and mRNA ( P <0.05). CONCLUSION: Dysregulation of apoptosis and activation of Fas/FasL system may play a key role in the pathogenesis of LPS induced acute liver injury in rats, which worsens the early stage acute liver injury. The protective effects of dexamethasone may obstruct the activation of Fas/FasL system and apoptosis of hepatocytes in rats with LPS induced acute liver injury and thus alleviate liver damage.