秋水仙碱拮抗肿瘤坏死因子α的肝毒性作用

The preventive effect of colchicine against the liver toxicity of tumor necrosis factorα

目的：探讨秋水仙碱（Ｃｏｌ）于在体条件下对重组人肿瘤坏死因子α（ＴＮＦ－α）所致动物肝毒性的影响。方法：将１８只雄性ＢＡＬＢ／ｃ小鼠随机分为Ａ～Ｃ３组，腹腔注射Ｄ－氨基半乳糖（ＧａｌＮ）７００ｍｇ／ｋｇ致敏，１ｈ后再次腹腔注射ＴＮＦ－α５０μｇ／ｋｇ诱发急性肝坏死。Ａ组小鼠于ＴＮＦ－α给药前１９和４ｈ分别腹腔注射生理盐水作为对照，Ｂ和Ｃ组则按相同时间分别灌服或腹腔注射Ｃｏｌ０．５ｍｇ／ｋｇ。给药８ｈ后测定小鼠血清丙氨酸转氨酶（ＡＬＴ）和甘氨酸结合胆汁酸（ＧＣＡ），并观察小鼠肝脏的病理改变。结果：ＴＮＦ－α注射８ｈ后Ｃ组ＡＬＴ及ＧＣＡ水平明显低于Ａ组（Ｐ＜０．０５），而Ｂ组与Ａ组无明显差别；Ｃ组小鼠肝脏病理损害程度亦较Ａ组和Ｂ组明显减轻（Ｐ＜０．０１）。结论：Ｃｏｌ对ＴＮＦα所致的动物肝毒性具有预防作用。

Objective: To determine the effect of colchicine(Col) against the liver toxicity of recombinant human tumor necrosis factorα(TNFα)in vivo. Methods: Eighteen male Balb/C mice were divided into three groups(6 mice in each group). Liver toxicity was induced by intraperitoneal administration of 50μg/kg of TNFα 1 h after the sensitization by Dgalactosamine (GalN), which was given intraperitoneally in a 700 mg/kg dosage. At 19 and 4 h prior to TNFα challenge, mice in group A were intraperitoneally administered with normal saline, while those in group B and C were intubated or intraperitoneally injected with 0.5 mg/kg of Col, respectively. Serum levels of alanine aminotransferase (ALT) and glycine conjugated bile acid (GCA) were detected and the pathologic changes of the liver were observed 8 h after the TNFα attack. Results: The serum levels of ALT and GCA in group C were apparently lower than those in group A (P<0.05), while those in group B and group A had no statistic difference. Mice in group C also had more slight hepatic pathological changes than those in group A and B (P<0.01). Conclusion: Col can prevent the liver toxicity induced by TNFα in vivo.