龙胆苦苷对D-氨基半乳糖联合脂多糖诱导的慢性肝损伤模型小鼠的保护作用

Protective effect of gentiopicroside on chronic liver injury mice induced by D-galactosamine combined with lipopolysaccharide

目的:研究龙胆苦苷对D-氨基半乳糖联合脂多糖诱导的慢性肝损伤模型小鼠的保护作用及其机制。方法:采用雄性C57BL/J小鼠随机分组并给药,每组按10 mL/kg腹腔注射D-氨基半乳糖脂多糖混合液,1次/2 d,造模6周,建立D-氨基半乳糖联合脂多糖诱导慢性肝损伤模型,同时每天按分组剂量给予对应的试药灌胃处理。检测血清中天门冬氨酸氨基转移酶(AST)和谷氨酸氨基转移酶(ALT)及肝组织中丙二醛(MDA)、超氧化物睦歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)及过氧化氢酶(CAT)的含量;计算肝脏及脾脏指数;HE染色观察肝组织病理学变化。结果:龙胆苦苷50 mg/kg、100 mg/kg均可显著降低小鼠血清ALT、AST含量和肝组织中MDA水平(P<0.05,P<0.01,P<0.001),升高肝组织中SOD、GSH-Px、CAT含量(P<0.05),显著改善小鼠的肝脏和脾脏指数(P<0.05,P<0.01,P<0.001);龙胆苦苷50 mg/kg、100 mg/kg组小鼠肝细胞条索状排列趋于正常,细胞坏死病变以及炎细胞浸润显著减少。结论:龙胆苦苷对D-氨基半乳糖联合脂多糖诱导的慢性肝损伤模型小鼠有较好的保护作用,其机制可能与增加机体免疫功能和调节氧化与抗氧化作用有关。

Objective:To study the protective effect of gentiopicroside on chronic liver injury induced by D-galactosamine combined with lipopolysaccharide in mice and its mechanism.Methods:Male c57BL/J mice were randomly divided into groups and given drugs.Each group was given 10 mL/kg of D-galactosamine lipopolysaccharide mixture intraperitoneally,once two days.For 6 weeks,the model of chronic liver injury induced by D-galactosamine combined with lipopolysaccharide was established,while the corresponding test drug was given daily by gavage at grouped doses.The contents of AST and ALT in serum and MDA,SOD,GSH-Px and CAT in liver tissues were detected.The indexes of liver and spleen were calculated.Hematoxylin-eosin staining was used to observe the pathological changes of liver tissues.Results:Both 50 mg/kg and 100 mg/kg gentiopicroside could significantly reduce the contents of ALT and AST in serum and the level of MDA in liver tissues(P<0.05);the contents of SOD,GSH-Px and CAT in liver tissues were increased(P<0.05,P<0.01,P<0.001);the indexes of liver and spleen in mice were significantly improved(P<0.05,P<0.01,P<0.001);in gentiopicroside 50 mg/kg and 100 mg/kg groups,the arrangement of hepatocytes tended to be normal,and cell necrosis and inflammatory cell infiltration decreased significantly.Conclusion:Gentiopicroside has a good protective effect on chronic liver injury induced by D-galactosamine combined with lipopolysaccharide in mice,which may be related to increasing the body′s immune function and regulating the oxidative and antioxidant effects of the organism.