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目的:观察四物合剂对化疗药物顺铂肝毒性的作用,并对其作用机制进行探讨。方法:小鼠腹腔注射顺铂,3·0mg/kg体重/日,连续7日,并灌饲四物合剂14日,观察血清丙氨酸氨基转移酶(ALT)活性、肝脏系数、肝匀浆中SOD、GSH-PX、GSH和MDA含量变化及肝线粒体中NADH脱氢酶复合体(复合体Ⅰ)和琥珀酸脱氢酶复合体(复合体Ⅱ)活性变化。结果:注射顺铂7日后小鼠肝脏中SOD和GSH-PX活性及GSH含量下降,MDA含量升高,同时给予四物合剂小鼠肝脏中SOD含量上升,GSH-PX活性及GSH含量、MDA含量均下降;顺铂小鼠肝线粒体中NADH脱氢酶复合体(复合体Ⅰ)活性升高,琥珀酸脱氢酶复合体(复合体Ⅱ)活性下降,四物合剂可减弱该反应。结论:顺铂模型小鼠肝组织细胞潜在抗氧化能力明显下降,四物合剂可改善此现象,其作用机制可能与升高机体内抗氧化酶活性、减少自由基生成有关。
OBJECTIVE: To observe the effect of Siwu Mixture on cisplatin hepatotoxicity of chemotherapeutic agents and to explore the mechanism of action. METHODS: Mice were intraperitoneally injected with cisplatin at a dose of 3.0 mg/kg body weight/day for 7 consecutive days and were fed with Siwu Mixture for 14 days. Serum alanine aminotransferase (ALT) activity, liver coefficient, liver homogenate were observed. Changes in SOD, GSH-PX, GSH, and MDA levels, and changes in NADH dehydrogenase complex (complex I) and succinate dehydrogenase complex (complex II) activity in liver mitochondria. RESULTS: After 7 days of injection of cisplatin, the activities of SOD and GSH-PX and the content of GSH decreased, and the content of MDA increased in mice liver. Simultaneously, SOD content in the liver of mice given Siwu Mixture was increased, GSH-PX activity, GSH content, and MDA content were increased. Both decreased; the activity of NADH dehydrogenase complex (complex I) was increased in liver mitochondria of cisplatin mice, and the activity of succinate dehydrogenase complex (complex II) was decreased. Siwu Mixture could weaken the reaction. Conclusion: The potential antioxidant capacity of liver cells in cisplatin-treated mice was significantly decreased. Siwu Mixture can improve this phenomenon. The mechanism may be related to the increase of antioxidant enzyme activity and reduction of free radical production in vivo.