满天星染料木黄酮对小鼠急性肝损伤的保护作用及机制  

Protective Effect and Mechanism of Genistein from Hydrocotyle sibthorpioides on Acute Hepatic Injury in Mice

作　　者：韦玲[1] 黄权芳[2] 林兴[1] 

机构地区：[1]广西医科大学,南宁530021 [2]广西中医药大学第一附属医院,南宁530023

出　　处：《中国实验方剂学杂志》2015年第4期102-106,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81260674);广西自然科学基金项目(2013GXNSFAA019146)

摘　　要：目的:研究满天星活性成分染料木黄酮对脂多糖(lipopolysaccharide,LPS)或D-氨基半乳糖(D-galactosamine,D-Gal N)诱导引起的小鼠急性肝损伤的保护作用及其机制。方法:雄性小鼠随机分为正常组、模型组、染料木黄酮低、中、高剂量组。正常组和模型组ip等容量生理盐水,染料木黄酮低、中、高剂量组分别腹腔注射0.5,1,2 mg·kg-1的染料木黄酮,每日1次。连续给药3 d后,除正常组外,其余各组小鼠ip LPS(50μg·kg-1)和D-Gal N(800 mg·kg-1),1.5 h后,眼眶血管丛取血,6 h后处死。采集肝脏组织,检测小鼠血清丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST),胆红素的水平;并检测各组小鼠肝组织中丙二醛(MDA),肿瘤坏死因子-α(TNF-α),一氧化氮(NO)含量及TNF-α,诱导型一氧化氮合酶(i NOS)mRNA,核因子(NF)-κB p65,半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)和B细胞淋巴瘤/白血病2(Bcl-2)表达情况;同时做组织学检查,观察肝组织的病理变化。结果:与模型组比较,染料木黄酮显著降低小鼠血清中AST,ALT活性,明显减轻组织病理损伤;可抑制NF-κB的激活,继而减少炎症因子TNF-α,NO和i NOS的水平。此外,染料木黄酮明显抑制Caspase-3的表达,提高Bcl-2的水平,提升胆红素的含量。结论:满天星染料木黄酮对小鼠急性肝损伤具有明显的保护作用,其机制与抑制NF-κB信号通路、减轻炎症反应有关。Objective： To investigate the protective effect and underlying mechanism of genistein from Hydrococyle sibthorpioides on lipopolysaccharide （LPS） /D-galactosamine （D-GalN） -induced acute hepatic injury in mice. Method： Male mice were randomly divided into normal group, model group, low-, middle-and high-doses of genistein-treated groups. The mice in the normal and model groups were given saline. The animals in the genistein-treated groups were administered intraperitoneally 0.5, 1, 2 mg ·kg^1 genistein once daily for 3 days. At the end of treatment, except the mice in the normal group, all mice were intraperitoneally injected with 50μg·kg^-1 LPS plus 800 mg·kg^-1 D-GaIN. Blood samples were collected from mice eyes 1.5 h after LPS/D-GalN administration, then the mice were killed and liver samples were dissected out after 6 h. The activities of serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and bilirubin, the contents of hepatic tumor necrosis factor-α（TNF-α）, nitric oxide （NO） and malandialdehyde （MDA）, as well as the expression of TNF-α, inducible nitric oxide synthase （iNOS） , nuclear factor （NF）-κB p65, Caspase-3 and B cell lymphoma/ leukemia-2 （Bcl-2） were detected. In addition, the damage of liver tissues was observed by light microscope. Result： Compared to the model control, treatment with genistein significantly decreased the AST and ALT activities, further increased the bilirubin level. Histologic examination showed that genistein markedly alleviated the mice livers tissue damage. Furthermore, genistein reduced the pro-inflammatory cytokines including TNF-α and NO/iNOS via inhibiting the NF-κB activity. In addition, genistein inhibited the expression of Caspase-3, enhanced levels of Bcl-2 and total bilirubin. Conclusion： Genistein could prevent LPS/D-GalN-induced acute liver damage in mice, and its underlying mechanisms were mainly due to its ability to block NF-κB signaling pathway for anti-inflammation response and attenu

关 键 词：染料木黄酮 满天星 脂多糖 D-氨基半乳糖 急性肝损伤 

分 类 号：R285.5[医药卫生—中药学]