NF-κB和TNF-α在暴发性肝衰竭肝组织中的表达及其意义

目的探讨NF-κB，TNF-α与暴发性肝衰竭发生、发展的关系及其意义。方法雄性Wistar大鼠腹腔注射D-GalN＋LPS制造暴发性肝衰竭模型，采用免疫组化方法动态观察肝组织中NF-κB p65蛋白和TNF-α表达情况。结果①动态观察了暴发性肝衰竭病理变化过程。②模型组NF-κB p65蛋白表达阳性细胞主要为肝细胞、枯否细胞。造模后4h、8h、12h时核阳性表达的细胞数逐渐增多，明显高于对照组。2h组主要是非实质细胞的胞质着色。而4h、8h、12h、24h组以肝细胞胞核着色为主。对照组不同时间点NF-κB p65蛋白表达无明显差异（P〉0．05）。模型组则随着肝细胞坏死程度的增加而增加（r=0．694，P〈0．01）。③随着肝细胞炎症坏死程度的增加，模型组肝细胞质TNF-α表达逐渐增加（r=0．896，P〈0．01），以肝细胞表达为主。对照组肝细胞质TNF-α表达较弱（P〉0．05）。④肝组织中NF-κB活化与TNF-α表达呈密切正相关（r=0．852，P〈0．01）。结论NF-κB和TNF-α参与了暴发性肝衰竭的发生发展。NF-κB可能是暴发性肝衰竭肝细胞炎症坏死过程中的关键环节。

EXPRESSION AND SIGNIFICANCE OF NF-κB AND TNF-α IN LIVER TISSUE oF FULMINANT HEPATIC FAILURE

Objective To investigate the relationship of NF-κB and TNF-α with the occurrence and development of fulminant hepatic failure （FHF） and significance. Methods The experimental model of FHF was established by injecting D-GaiN and lipopolysaccharide （LPS） into masculine Wistar rats. The expression of NF-κB p65 and TNF-α in the liver tissue was evaluated by immunohistochemistry. Results ①The pathological change process of FHF induced by D-GalN ＋ LPS was dynamically observed. ②The positive staining cells of NF-κB p65 protein were mainly hepatocytes and Kupffer cells in the model group. The number of the nucleus positive staining cells was gradually increased in 4, 8 and 12h groups. The positive staining was seen mainly in the cytoplasm of nonparenchyreal cells at 2h, but mainly in hepatocyte nuclei at 4, 8, 12 and 24 h. The expression of NF-κB p65 protein showed no obvious difference at different time points in the control group （P 〉 0. 05 ）, but increased with the development of hepatocyte necrosis in the model group （r = 0. 694, P 〈 0. 01 ） . ③The expression of TNF-α in the hepatoeyte cytoplasm was gradually increased in the model group with the development of hepatocyte inflammation and necrosis （r =0. 896, P 〈0. 01 ） . It was mainly expressed in hepatocytes. The expression of TNF-α in hepatocyte cytoplasm was relatively weak in the control group （P 〉 0. 05） . ④There was a close positive correlation between the activation of NF-κB and the expression of TNF-α in the liver tissue （r =0. 852, P 〈0.01 ） . Conclusion NF- κB and TNF-α may take part in the occurrence and development of FHF. NF-κB may play a key role in the hepatocyte inflammation and necrosis process of FHF.