黄药子总皂苷对小鼠的肝毒性及其机制  

Hepatotoxicity of Total Saponins Extracted from Dioscorea Bulbifera in Mice and Its Mechanism

作　　者：梁玉琼[1] 黄庆 时乐[3] 徐立[3] 覃日宏[1] 汪磊[1] LIANG Yuqiong;HUANG Qing;SHI Le;XU Li;QIN Rihong;WANG Lei(Experiment Teaching Center,Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine,Nanning 530222,Guangxi,China;Department of Pharmacy,The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China;Pharmaceutical Sciences College,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China)

机构地区：[1]广西中医药大学赛恩斯新医药学院实验教学中心,广西南宁530222 [2]广西中医药大学第一附属医院药学部,广西南宁530023 [3]南京中医药大学药学院,江苏南京210023

出　　处：《中华中医药学刊》2020年第10期240-244,I0048,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：江苏高校优势学科建设工程项目(2011ZYX4-005);广西高校中青年教师基础能力提升项目(2018KY0836)。

摘　　要：目的探讨黄药子总皂苷(TSRD)连续给药对小鼠肝毒性及其机制。方法昆明种小鼠,按照分组灌胃给予TSRD 40 g/kg,分别连续给药10、20、30 d。检测肝系数,血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性,肝组织中Na^+-K^+-ATP酶、Ca^2+-Mg^2+-ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽S转移酶(GST)、琥珀酸脱氢酶(SDH)活性及丙二醛(MDA)、羟脯氨酸(Hyp)含量,HE染色法观察肝组织病理改变,Western蛋白质印迹法检测肝组织细胞色素P450(CYP)2E1、核因子相关因子2(Nrf2)表达。结果与各自空白对照组相比,各给药组小鼠肝系数升高(P<0.01);30 d给药组小鼠血清ALT、AST水平升高(P<0.05,P<0.01),20、30 d给药组小鼠肝组织Na^+-K^+-ATP、Ca^2+-Mg^2+-ATP酶、SOD、GST和SDH活性降低(P<0.01,P<0.05),MDA含量升高(P<0.05);HE染色显示,各给药组小鼠肝细胞有轻微或轻度嗜酸变性、坏死;TSRD可显著增强20 d给药组和30 d给药组小鼠肝组织CYP2E1、Nrf2表达(P<0.05,P<0.01)。结论TSRD长期给药后对小鼠肝脏具有一定的毒性,其机制可能与氧化应激损伤,诱导肝组织Nrf2及CYP2E1表达有关。Objective To observe the hepatotoxicity of total saponins extracted from Dioscorea bulbifera(TRSD)in mice and its mechanism.Methods Sixty Kunming mice were randomly divided into six groups(10 d control group,10 d TSRD group,20 d control group,20 d TSRD group,30 d control group,30 d TSRD group).Each group was orally administered with TSRD(40 g/kg body weight)or distilled water once a day for 10,20 and 30 days.The serum was sampled to detect levels of ALT and AST.The activities of Na^+-K^+-ATPase,Ca^2+-Mg^2+-ATPase,superoxide dismutase(SOD),glutathione S-transferase(GST),succinate dehydrogenase(SDH)and the contents of metahne dicarboxylic aldehyde(MDA)and hydroxyproline(HYP)in liver tissue of mice were detected.Liver histopathology was revealed by HE staining.The protein expressions of cytochrome P450(CYP2E1)and NF-E2-related factor 2(Nrf2)in the liver were analyzed by Western blotting.Results Compared with those of the corresponding control groups,liver indexes of 10,20,30 d TSRD groups were increased(P<0.01).The levels of ALT and AST in 30 d TSRD group were increased(P<0.05,P<0.01).The activities of Na^+-K^+-ATPase,Ca^2+-Mg^2+-ATPase,SOD,GST and SDH were decreased(P<0.01,P<0.05)and the content of MDA of liver tissue in 20,30 d TSRD groups was increased(P<0.05).The liver cells had a slight or mild acidophilic degeneration and necrosis in 20,30 d TSRD groups.Preliminary mechanism research showed the protein expressions of CYP2E1 and Nrf2 were increased(P<0.05,P<0.01).Conclusion TSRD may induce liver injury in mice after long-term administration and the mechanism is possibly related to oxidative damage and increases the protein expressions of CYP2E1 and Nrf2.

关 键 词：黄药子总皂苷 肝毒性 氧化应激 细胞色素P4502E1 核因子相关因子2 

分 类 号：R285.5[医药卫生—中药学]