油橄榄叶醇提取物对D-半乳糖胺/脂多糖致小鼠急性肝损伤的保护作用及其作用机制

Protective effects and related mechanism of olive leaf methanolic extract against acute liver injury in mice induced by D-galactosamine/lipopolysaccharide

研究油橄榄叶醇提取物(OLME)对D-半乳糖胺/脂多糖诱导小鼠肝损伤的保护作用。昆明种小鼠按体质量随机分为6组,即空白对照组、模型对照组、阳性对照组(联苯双酯200 mg/kg·d)、OLME低、中、高剂量组(200、400、800 mg/kg·d)。每天给药1次,连续给药14 d,末次给药1 h后,除正常组外其余各组用600 mg/kg·BW D-半乳糖胺和40μg·kg^(^(-1))脂多糖腹腔注射以复制小鼠急性肝损伤模型,末次给药12 h后,摘眼球取血,取材。用生化法测定小鼠血清中谷氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性,用试剂盒测定各组小鼠肝匀浆中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL^(-1)β)和白细胞介素-6(IL-6)等炎性因子的表达水平以及半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)和半胱氨酸天冬氨酸蛋白酶-8(Caspase-8)活性。与模型组比较,OLME中高剂量组小鼠血清中ALT和AST活力显著降低(p<0.05),肝组织中MDA、TNF-α、IL-1β和IL-6含量显著降低而SOD活力显著升高(p<0.05),但OLME对GSH-Px改善作用不明显,仅OLME高剂量有一定效果;OLME低、中、高剂量均能显著降低caspase-3和caspase-8活性(p<0.05)。OLME对D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤具有较好的保护作用。

The aim of this study was to investigate the protective effects of olive leaf methanolic extract（ OLME） on acute liver injury induced by D-galactosamine/lipopolysaccharide（ LPS） in mice. Methods： Kunming mice were randomly divided into six group： normal group,model group,positive group（ bifendate 200 mg·kg-1）,and OLME at a dose of 200,400,and 800 mg·kg-1（ different experimental groups）.The drug was administered once a day for consecutively 14 d.The acute liver injury model was induced by intraperitoneal injection of 600 mg·kg-1D-galactosamine and 40 μg·kg-1LPS within one hour after last administration,the normal group receiving the same volume of saline. Twelve hours after the last administration,blood and tissues were collected from each mouse. Serum ALT and AST levels were measured by biochemical method. The activities of SOD,GSH-Px,caspase-3 and caspase-8 and the contents of MDA,TNF-α,IL-1β,and IL-6 in liver tissue were measuredusing kits.Results： Being Compared with the model group,OLME（ 400 and 800 mg·kg-1） treatment significantly reduced serum ALT and AST activities（ p 〈 0.05）,reduced MDA contents in liver homogenate,and increased SOD activity（ p 〈 0.05）.OLME at400 and 800 mg·kg-1dose groups significantly decreased TNF-α,IL-1β and IL-6 contents（ p 〈 0.05）.However,the improved effect of OLME on GSH-Px was not obvious,only high OLME dose had certain effect.OLME at 200,400 and 800 mg·kg-1dose groups significantly decreased caspase-3 and caspase-8 activities（ p 〈 0.05）.Conclusion： OLME plays good protective effects to mice with acute liver injury induced by intraperitoneal injection of D-galactosamine and LPS.