白细胞介素-18抗体在急性免疫性肝损伤中的保护作用研究

Protective Effects of IL-18 Antibody on Acute Immunological Liver Injury

目的探讨白细胞介素-18抗体对急性免疫性肝损伤小鼠的保护作用。方法昆明种小鼠给予不同剂量白细胞介素-18抗体。12 d后处死小鼠,测定小鼠肝脏、脾脏、胸腺系数,测定小鼠血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、白细胞介素-18(IL-18)、白细胞介素-6(IL-6)、α-肿瘤坏死因子(TNF-α)含量,光镜下观察肝组织细胞结构的改变。结果模型组肝细胞损伤明显,处理组较轻。模型组小鼠血清AST、ALT、IL-18、IL-6、TNF-α含量比对照组明显升高,P<0.05。与模型组相比,处理组小鼠血清AST、ALT、IL-18、IL-6、TNF-α含量降低,以大剂量IL-18抗体组明显,P<0.05。结论应用IL-18抗体对小鼠急性免疫性肝损伤有保护作用,并可能是通过抑制IL-6、TNF-α的作用来实现的。

Objective To investigate the role of IL-18 and evaluate the protective effect of monoclonal antibody against IL-18 in acute immunological liver injury in mice. Methods Mice were injected intraperitoneally with monoclonal antibody against IL-18. After 12 days, sera of mice were sampled for measuring ALT and AST using spectrophotography, measuring IL-18, IL-6 and TNF-α. Results The sera IL-18 ,IL-6 and TNF-α levels were elevated in acute immunological liver injury in mice. High dose antibody intervention groups remarkably inhibitited the serum level of IL-18 ,IL-6 and TNF-α（ P 〈 0. 05 ）. The serum levels of ALT and AST in high dose antibody intervention groups were lower than those of the controls （P 〈 0. 05 ）. Compared with model groups, antibody intervention groups relieved liver constitution damage. Conclusion IL-18 plays an important role in acute immunological liver injury in mice. Role of IL-18 was closely correlated with IL-6 and TNF-α in immunological liver injury. Monoclonal antibody against IL-18 relieved liver constitution damage. Therefore, antibody groups can protect mice from immunological liver injury.