乔松素对对乙酰氨基酚诱发的肝损伤小鼠模型的保护作用

目的探索乔松素(PIN)对对乙酰氨基酚(APAP)诱发肝损伤小鼠模型的保护作用。方法50只健康雄性C57BL/6J小鼠随机分成空白组、PIN(50 mg/kg)组、APAP(300 mg/kg)模型组、PIN(30 mg/kg)+APAP(300 mg/kg)组和PIN(50 mg/kg)+APAP(300 mg/kg)实验组,每组各10只。各组采取灌胃给药,空白对照组和模型组给予等量的生理盐水,PIN组及PIN+APAP组每日给药1次,连续给药7 d。末次给药2 h后,模型组和PIN+APAP组腹腔注射APAP 300 mg/kg 1次,空白组和PIN组腹腔注射等量生理盐水。收集血清,检测ALT、AST水平,肝组织匀浆检测丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽(GSH)生化指标,HE染色观察肝脏组织病理情况。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与空白组比校,APAP(300 mg/kg)模型组的ALT、AST水平显著升高(P<0.01),模型构建成功;PIN(30 mg/kg)+APAP(300 mg/kg)及PIN(50 mg/kg)+APAP(300 mg/kg)组的ALT、AST与APAP(300 mg/kg)模型组相比均显著降低(P值均<0.01)。与空白组比校,APAP(300 mg/kg)模型组小鼠肝脏中MDA的水平显著升高(P<0.01),且SOD活性及GSH水平显著降低(P<0.01);与APAP(300 mg/kg)模型组比较,PIN(30 mg/kg)+APAP(300 mg/kg)及PIN(50 mg/kg)+APAP(300 mg/kg)组的小鼠肝脏中MDA的水平显著降低(P值均<0.05),且SOD活性及GSH水平显著升高(P值均<0.05)。组织病理观察显示PIN可明显改善APAP对肝组织的损伤,使肝组织形态相对正常。结论PIN对APAP诱发的小鼠肝损伤具有明显的保护作用,其保护作用可能与抑制肝脏氧化应激相关。

Protective effect of pinocembrin in a mouse model of liver injury induced by acetaminophen

Objective To investigate the protective effect of pinocembrin(PIN)in a mouse model of liver injury induced by acetaminophen(APAP).Methods A total of 50 healthy male C57BL/6J mice were randomly divided into blank group,PIN(50 mg/kg)group,APAP(300 mg/kg)model group,PIN(30 mg/kg)+APAP(300 mg/kg)experimental group,and PIN(50 mg/kg)+APAP(300 mg/kg)experimental group,with 10 mice in each group.The mice in the blank group and the model group were given an equal volume of normal saline by gavage,and those in the PIN group and the PIN+APAP groups were given PIN by gavage once a day,for 7 consecutive days.At 2 hours after the last administration,the mice in the model group and the PIN+APAP groups were given intraperitoneal injection of APAP 300 mg/kg once,and those in the blank group and the PIN group were given intraperitoneal injection of an equal volume of normal saline.Serum samples were collected to measure the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST);liver tissue homogenate was prepared to measure the biochemical parameters of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH);HE staining was used to observe liver histopathology.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the blank group,the APAP(300 mg/kg)model group had significant increases in the activities of ALT and AST(P<0.01),suggesting that a model was successfully established,while the PIN(30 mg/kg)+APAP(300 mg/kg)group and the PIN(50 mg/kg)+APAP(300 mg/kg)group had significant reductions in the levels of ALT and AST(P<0.01).Compared with the blank group,the APAP(300 mg/kg)model group had a significant increase in the level of MDA and significant reductions in SOD activity and GSH level in the liver(P<0.01);compared with the APAP(300 mg/kg)model group,the PIN(30 mg/kg)+APAP(300 mg/kg)group and the PIN(50 mg/kg)+APAP(300 mg/kg)group had a significant reduction in the level of MDA and significant increases in SOD activity and GSH level in the liver(P<0.05).Histopathological observation showed that PIN significantly improved liver injury caused by APAP and helped to maintain normal liver histomorphology.Conclusion PIN exerts a marked protective effect on liver injury induced by APAP,possibly by inhibiting oxidative stress in the liver.