波棱甲素纳米混悬剂对D-半乳糖胺诱导的小鼠急性肝损伤的保护作用

Protective Effect of Herpetrione Nanosuspension Against Acute Liver Injury Induced by D-galactosamine in Mice

目的研究波棱甲素纳米混悬液(HNS)对D-半乳糖胺(D-GalN)诱导的小鼠急性肝损伤的保护作用,并与波棱甲素普通混悬剂(HS)进行比较。方法小鼠每日给药2次,连续给药3.5 d后,一次性腹腔注射D-GalN 800 mg.kg-1造成急性肝损伤模型,20 h后取血清测定丙氨酸基转移酶(ALT)、天冬氨酸氨基转移酶(AST)值。结果 HNS各个剂量组均能显著降低中毒小鼠ALT、AST含量,HS仅高剂量组ALT、AST值显著降低,且同等剂量下,HNS各组均明显优于HS各组;病理检查结果显示,波棱甲素具有明显的保肝作用。结论 HNS对D-GalN诱导的小鼠急性肝损伤具有明显的保护作用,且作用明显优于普通混悬剂。其机制可能在于将其制成纳米混悬剂之后,粒径减小,表面积增大,体内吸收增加,从而使它的药效作用增强。

OBJECTIVE To study the protective effect of herpetrione nanosuspension（HNS） against acute liver injury induced by D-GaIN in mice. METHODS Mice were administered with drugs by gastric gavage twice a day for 3.5 d. One hour after the last administration, except those in the group of blank control, mice were intraperitoneally injected with D-GaIN 800 mg.kg-1. Blood samples were collected 20 h after administration, and the levels of ALT and AST in serum were measured. Histopathological examination of liver tissue was also performed. RESULTS Each dosage group of HNS could significantly decrease the serum ALT and AST levels, while only high dosage group of HS had similar effect. In addition, the effects of all HNS groups were better than those of HS groups at the same dose. The result of pathology determination showed that HNS could markedly ameliorate the liver damage induced by D-GalN. CONCLUSION HNS could significantly protect against acute liver injury. induced by D-GaIN in mice, and its effect was superior than that of HS. The mechanism is probably that HNS particle diameter is extremely small, which results larger surface area and better absorption in vivo, thus its therapeutic effect can possiblely be enhanced.