肝宝胶囊防治抗结核药物性肝损伤的作用机理初探

Effect and Mechanism Study of Ganbao Capsule on the Liver Injury Induced by Anti-Tuberculosis Drugs

目的:探讨肝宝胶囊对抗结核药物引起肝损伤的保护作用及可能机制。方法:在灌胃利福平300 mg/kg+吡嗪酰胺625 mg/kg引起大鼠肝损伤的同时灌胃肝宝胶囊以考察其预防肝损伤作用。小鼠在灌胃利福平300 mg/kg一周形成肝损伤模型后,再灌胃给予肝宝胶囊三周以评价其对肝损伤的治疗作用。结果:与正常对照组比较,模型对照组大鼠血清ALT、AST、TBil、DBil、TBA水平及肝脏TC、TG水平均显著升高,其血清TP水平下降(P<0.01),肝脏组织出现明显的脂肪变;与模型对照组比较,其中肝宝胶囊8 g/kg可以显著抑制利福平加吡嗪酰胺引起大鼠血清ALT、AST、TBil、DBil、TC以及TG水平的升高,升高血清HDL-C、TP以及Alb水平,降低血清LDL-C水平、肝脏TC以及TG含量(P<0.05或P<0.01),改善肝脏病理组织结构。结论:利福平可能通过影响肝脏脂质分布引起肝脏脂质堆积增加,诱导胆红素以及胆汁酸大量合成,导致肝功能受损;利福平与吡嗪酰胺联用后其肝脏脂质堆积程度得到减轻的原因可能与吡嗪酰胺能够减少TG向肝脏转运有关。肝宝胶囊能够调节血脂代谢,减少肝脏脂质堆积,从而减轻利福平、利福平与吡嗪酰胺联用所引起的肝损伤,其详细作用机制有待进一步深入研究。

Objective:To explore the protective effect and possible mechanism of Ganbao capsule on the liver injury induced by anti-tuberculosis drugs.Methods:Rats with liver injury were induced by intragastric administration of 300 mg/kg rifampicin combined with 625 mg/kg pyrazinamide and were treated with Ganbao capsule to observe its protecitve effect on liver injury.Mice with liver injury were induced by intragastric administration of 300 mg/kg rifampicin for 4 weeks,from the 8 th day,Ganbao capsule was given to mice for 3 weeks.Results:Compared with the control group,the serum levels of ALT,AST,TBil,DBil,TBA,the levels of TC and TG in liver tissues were significantly increased in the model group,the serum TP level was decreased(P<0.01),obvious adipose changes were observed in liver tissues.Compared with the model group,8.0 g/kg Ganbao capsule significantly inhibited the elevation of serum ALT,AST,TBil,DBil,TC and TG caused by rifapine plus pyrzine in rats,increased the serum levels of HDL-C,TP and Alb,reduced their serum LDL-C level,reduced the liver levels of TC and TG(P<0.05 or P<0.01),and improved the structure of liver pathological tissue.Conclusion:Rifampicin may damage the liver by enhancing the synthesis of bilirubin and bile acid via increasing the accumulation of lipid in the liver.Pyrazinamide may inhibit the accumulation of liver lipid increased by rifampicin,through reducing the transport of TG to liver.Ganbao capsule can regulate the blood lipid metabolism,reduce the liver lipid accumulation,thus reduce the liver injury caused by rifampicin or rifampicin combined with pyrazinamide.The detailed mechanism needs to be further studied.