目的:研究竹节参总皂苷对异烟肼和利福平合用致小鼠肝损伤的保护作用。方法:灌胃异烟肼(75mg/kg)、利福平(100mg/kg)7d以复制小鼠肝损伤模型。40只雄性Bab1c小鼠随机分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、水飞蓟宾(50mg/kg)组与竹节参总皂苷高、低剂量(100、50mg/kg)组,复制模型的同时灌胃给予相应药物,每天1次,连续7d。测定小鼠肝脏指数、血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性、肝匀浆中丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH.Px)活性及mRNA的表达情况,并作小鼠一般情况与肝组织病理学观察。结果:与正常对照组比较,模型组小鼠肝脏指数显著升高,肝组织ALT、AST活性显著增强,sOD、GSH.Px活性显著减弱,MDA含量显著增加,GSH—Px和SOD。mRNA表达显著减弱(尸〈0.01或P〈0.05)。与模型组比较,竹节参总皂苷高、低剂量组小鼠肝脏指数显著降低,肝组织ALT、AST活性显著减弱,SOD:、GSH.Px活性显著增强,MDA含量显著减少,GSH—PX和SOD:mRNA表达显著增强(P〈0.01或P〈0.05)。正常对照组小鼠肝脏外观正常,肝小叶结构清楚,肝细胞索排列整齐,肝细胞轻微水肿,核结构清晰,肝窦正常;模型组小鼠肝脏明显肿大,质脆,边缘钝而厚,表面呈黄褐色颗粒状,肝细胞弥漫性水肿,胞浆疏松化,胞质色淡,肝细胞点状坏死,散在有炎性细胞浸润;竹节参总皂苷高、低剂量组小鼠肝大体与肝组织病理学均明显改善。结论:竹节参总皂苷对异烟肼和利福平合用致小鼠肝损伤具有明显的保护作用,其机制可能与其抗脂质过氧化有关。
OBJECTIVE: To study the protective effects of total saponins of Panax japonicus on mice liver injury induced by isoniazid and rifampicin. METHODS: Mice liver injury model was induced by intragastric administration of isoniazid (INH 75 mg/ kg) and rifampicin (RFP 100 mg/kg). 40 male Bablc mice were randomly divided into normal control group (constant volume of normal saline) , model group (constant volume of normal saline), silymarin group (50 mg/kg), total saponins of P. japonicus low-dose and high-dose groups(100, 50 mg/kg). Model mice were given relevant medicines intragastrically once a day for consecu- tive 7 days. Then liver index, the activities of ALT and AST in serum, MDA content, the activities and mRNA expressions of SOD and GSH-PX in liver homogenate were investigated. General information and liver histopathology were observed. RESULTS: Compared with normal control group, liver index of mice, the activities of ALT and AST in liver tissue, the content of MDA jn model group increased significantly, while the activities and mRNA expression of SOD2 and GSH-PX decreased significantly(P〈0.05 or P〈0.01 ). Compared with model group, liver index of mice, the activities of ALT and AST in liver tissue, the content of MDA in P. japonicus low-dose and high-dose groups decreased significantly, while the activities and mRNA expression of SOD and GSH-PX increased significantly(P〈0.05 or P〈0.01). Normal appearance of liver, clear structure of hepatic lobules, ordered hepatic cords, mild edema of hepatic cell, clear nuclear structure and normal sinus hepaticus were observed in normal control group. Obvious swelling of liver, crispy, blunt and thick liver edge, yellowish-brown granular appearance, diffuse edema of liver cell, loose endo- chylema, kytoplasm light in color, hepatocyte spotty necrosis and scatterredinflammatory cell infiltration were observed in model group. Liver and hepatic histopathology of mice were improved significantly in total saponins of P. japonicus hi