抗氧自由基药物对急性肝功能衰竭大鼠血清IL-18的影响

Effect of anti-oxidative drugs on serum IL-18 levels in rats with acute liver failure

目的了解IL-18与急性肝功能衰竭(AHF)的关系,探讨不同剂量还原型谷胱甘肽(GSH)治疗AHF的疗效。方法 Wister雄性大鼠42只随机分组,造模。空白对照(N)组(n=6)不予任何处理;模型对照(MG)组(n=12)每日静脉注射生理盐水,共5 d;大剂量治疗(GSH1)组(n=12)、小剂量(GSH2)组(n=12)每日分别静脉注射GSH 600 mg/kg、200 mg/kg,共5 d。于造模后24 h、48 h、72 h、7 d各组测定血清ALT、AST及IL-18值。结果各组大鼠造模后,24 h血清ALT、AST明显升高,48 h血清ALT、AST达到最高水平,以后各组存活大鼠血清ALT、AST逐渐下降,7 d时与N组相比差异仍有统计学意义(P<0.05),GSH1组血清AST与N组相比差异无统计学意义(P>0.05),而GSH1组、GSH2组与MG组相比24 h、48 h有统计学意义(P<0.05),72 h、7 d差异无统计学意义(P>0.05)。GSH1组和GSH2组相比,ALT 24 h、48 h有统计学意义(P<0.05),AST 48 h有统计学意义(P<0.05),两者其余时点差异无统计学意义(P>0.05)。各组大鼠造模后,24 h血清IL-18明显升高,48 h达最高水平,以后各组存活大鼠血清IL-18逐渐下降,7 d时仍高于N组(P<0.05)。GSH1组、GSH2组与MG组相比,48 h、72 h、7 d差异有统计学意义(P<0.05),24 h差异无统计学意义(P>0.05),GSH1组与GSH2组相比48 h差异有统计学意义(P<0.05),其余时点差异均无统计学意义(P>0.05)。结论 IL-18与AHF关系密切,IL-18可作为AHF的监测指标之一;早期应用大剂量抗氧自由基药物GSH能明显改善AHF大鼠的肝功能,促进受损肝细胞修复、再生。

Objective To investigate the relationship between interleukin-18（IL-18）and acute hepatic failure（AHF）in rats,and to study the efficacy of different doses of reduced glutathione（GSH）in treatment of AHF.Methods Thirty-six Wister male rats were used and were randomly divided into three groups（12 rats in each group）：model control group（MG group,intravenous injection of saline daily for 5 days）,high-dose therapy group（GSH1 group,intravenous injection of GSH 600 mg/kg daily for 5 days）,low-dose therapy group（GSH2 group,intravenous injection of GSH 200 mg/kg daily for 5 days）.Six Wister male rats were studied as blank control（N group,not treated）.Serum ALT,AST,and IL-18 values were detected at 24 h,48 h,72 h,7 d after treatment.Results Serum ALT,AST levels were significantly elevated at 24 h,reached peak levels at 48 h,and then gradually decreased in three model groups.The differences in ALT,AST between N group and three model groups were still significant at 7 d（P 0.05）.There was no significant difference in AST between GSH1 and N group（P 0.05）.The difference in AST among GSH1 group,GSH2 group,and MG group was significant at 24 h and 48 h（P 0.05）,but not so significant at 72 h and 7 d（P 0.05）.The difference in ALT between GSH1 group and GSH2 group was significant at 24 h and 48 h（P 0.05）,the difference in AST was significant at 48 h（P 0.05）,with no significant difference at other time points（P 0.05）.Serum IL-18 of rats in each treated group were significantly elevated at 24 h and peaked at 48 h.In each group serum IL-18 gradually decreased,remained higher than normal at 7 d（P 0.05）.Conclusions Serum IL-18 closely correlate with AHF,it might be used as one of the indicators for monitoring AHF.Early use of large doses of anti-oxidative drug GSH could significantly improve liver function in the AHF rats and promote repair and regeneration of impaired liver cells.