抗TNF-α单抗对刀豆蛋白A诱导急性肝损伤的保护作用

The Protective Effect of Monoclonal anti-TNF-αAntibody against Acute Hepatic Injury Induced by ConA in Mice

为探讨ＴＮＦ－α在刀豆蛋白Ａ（ＣｏｎＡ）诱导的肝损伤中的作用，在ＣｏｎＡ诱导的小鼠急性肝损伤模型上，观察血浆ＴＮＦ－α含量、ＡＬＴ活性、光镜和电镜下肝组织病理变化及应用抗ＴＮＦ－α单抗的肝损伤阻断作用。结果发现，与正常对照组比较，模型组ＴＮＦ－α、ＡＬＴ明显增高［分别为（０．１９±０．０６）ｎｇ／ｍｌ，（１４１４±５６７）Ｕ／Ｌ，均为Ｐ＜０．０１］，肝损伤在光镜、电镜下表现为肝细胞凋亡和坏死；抗ＴＮＦ－α单抗组的ＴＮＦ－α、ＡＬＴ分别较模型组和无关单抗组明显降低，未见肝细胞凋亡和坏死。结果表明：肝细胞凋亡可能为ＣｏｎＡ诱导肝细胞死亡的机制；ＴＮＦ－α在ＣｏｎＡ性肝损伤模型中起重要的介导作用；抗ＴＮＦ－α单抗可以阻断ＣｏｎＡ性肝损伤的发生，即有肝细胞保护作用。

To study the effect of monoclonal anti-TNF-α antibody on the concanavalin (ConA) -induced liver injury, the changes in plasma levels of alanine aminotransferase (ALT), tumor necrosis factor-α (TNF- α) and histopathology by light and electron microscopy were observed in the model of acute liver injury in mice induced by ConA as well as the protective effect of monoclonal anti-TNF-α antibody against hepatic injury in- vestigated. The results showed that plasma TNF-α and ALT levels in the model group [ (0. 19±0.06) μg/L and (1414±567) U/L] were significantly higher than those in the control group (P<0.01). Hepatic injury was characterized by apoptosis and necrosis of hepatic cells; Plasma TNF-α and ALT levels in the monoclonal anti-TNF-α antibody group were significantly lower than those in the model group and the group of the insignif- icant monoclonal antibody. Pathologic examination gave no evidence for apoptosis and necrosis. These results indicated that apoptosis might be an important mechanism of liver cell death induced by ConA in vovo. TNF-α has an important effect on this model; Monoclonal anti-TNF-α antibody can prevent hepatic injury indued by ConA.