目的: 观察三七总皂苷(PNS)对异烟肼(INH)和利福平(RFP)合用所致小鼠药物性肝损伤的保护作用及其机制。 方法: 小鼠随机分为正常组、模型组、PNS低、中、高剂量组(100,200,400 mg·kg-1)、和联苯双酯组(200 mg·kg-1)。采用INH和RFP合用复制小鼠药物性肝损伤模型,分光光度法测定血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST),肝匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)含量;HE染色法观察肝组织病理学变化,分析三七总皂苷的保肝作用及其可能机制。 结果: PNS中、高剂量组肝脏指数[(70.845.93),(66.384.33)mgg-1]低于模型组[(83.186.12)mgg-1](P〈0.05或P〈0.01);PNS低、中、高剂量组ALT[(89.7112.13),(79.5812.54),(65.8613.82)U·L-1,AST(101.5414.61),(83.709.85),(69.4715.41)U·L-1]水平低于模型组ALT[(102.6313.83)U·L-1,AST(117.0516.81)U·L-1](P〈0.05或P〈0.01),PNS中、高剂量组[MDA(7.801.21),(7.071.17)nmol·mg-1]含量低于模型组[(9.621.68)nmol·mg-1](P〈0.05或P〈0.01),PNS中、高剂量组[SOD(119.6914.32),(129.7220.22)U·mg-1,GSH-Px(108.0217.07),(112.7217.54) U·mg-1]活性高于模型组[SOD(101.7516.18)U·mg-1,GSH-Px(85.2314.44)U·mg-1](P〈0.05或P〈0.01)。肝组织HE染色显示PNS能显著减轻肝损伤程度。结论: 三七总皂苷对药物性肝损伤小鼠具有一定的保护作用,其机制可能与其抗氧化作用有关。
Objective: To investigate the protective effect and mechanism of saponins of Panax notoginseng (PNS) on drug-induced liver injury in mice. Method: Mice were randomly divided into six groups,control group,model group,low,middle,high-dose (100,200,400 mg kg-1) of PNS and bifendate group (200 mg kg-1). The model of drug-induced liver injury was induced by intragastric administration of isoniazid (INH) and rifampin (RFP) in mice. The levels of alanine aminotransferase (ALT),aspartate transaminase (AST) in serum and the content of superoxide dismutase (SOD),malondialdehyde(MDA),glutathione peroxidase (GSH-Px) in liver homogenate were assayed by spectrophotometry. The pathological changes of hepatic tissues were observed by hematoxylin and eosin (HE) staining. Result: The liver index (70.845.93),(66.384.33) mg g-1 of in PNS middle,high-dose groups was lower than that (83.186.12) mg g-1in the model group(P〈0.05 or P〈0.01). Compared with the model group,the levels of ALT (89.7112.13),(79.5812.54),(65.8613.82) U L-1 and AST (101.5414.61),(83.709.85),(69.4715.41) U L-1 in PNS low,middle,high-dose groups were significantly decreased(P〈0.05 or P〈0.01). The content of MDA (7.801.21),(7.071.17) nmol mg-1in PNS middle,high-dose groups was also lower than that (9.621.68) nmol mg-1in the model group(P〈0.05 or P〈0.01),while the activity of SOD (119.6914.32),(129.7220.22) U mg-1 and GSH-Px (108.0217.07),(112.7217.54) U mg-1 in PNS middle,high-dose groups was higher than that in the model group(P〈0.05 or P〈0.01). Hepatic tissues stained with HE showed that PNS could remarkably relieve liver injury. Conclusion: PNS has protective effect on drug-induced liver injury in mice,which may be related to antioxidant effect.