顺铂和卡铂致小鼠肝损害的实验研究

Study on the liver injuries induced by cisplatin and carboplatin in mice

目的探讨顺铂、卡铂致小鼠肝损害的时间及损伤机制。方法将90只小鼠分别尾静脉注射顺铂17mg／kg、卡铂67mg／kg及0．9％氯化钠注射液，分别于给药第3、7、11、14天测定各组小鼠血清生化指标、肝组织氧化及抗氧化指标，检查肝组织病理学改变。结果两实验组在给药第3天的病理切片即出现肝细胞脂肪变性，顺铂组尚有肝细胞点状坏死，周围有炎性细胞；两实验组天冬氨酸氨基转氨酶和碱性磷酸酶明显高于对照组（均P〈0．01），顺铂组丙氨酸氨基转氨酶明显高于对照组和卡铂组；两实验组氧化指标丙二醛明显高于对照组（均P〈0．01），抗氧化成分还原型谷胱甘肽明显低于对照组（均P〈0．01）。结论顺铂、卡铂在给药第3天即可引起肝组织损伤，顺铂致肝损伤的程度明显重于卡铂。

Objective To study the time the liver injuries appeared,the different level of liver injury induced by injecting Cisplatin and Carboplatin in mice and the possible mechanisms of the liver injury. Methods Mice were intravenously given, Cisplatin（ 17 mg/kg）, Carboplatin（ 67 mg/kg） respectively. In the 3th ,7th, 11th and 14th day after injecting the medicines, the serum biochemistry parameters, oxidation and antioxidation parameters of liver and histopathologlc change in hepatic tissue were observed. Results HE stain showed that fatty degeneration of hepatocyte in the two experiment groups in the 3th day after injecting medicines, and hepatocellular spotty necrosis, and inflltration of inflammatory cells arroud the necrotic liver were found in, Cisplatin group. The level of aspartate aminotransferase and alkaline phosphatase in the two experiment groups increased significantly compared with those in the control （group P 〈 0.01 ） , and alanine aminotransferase in Cisplatin group increased significantly（ P 〈 0.01 ） ,compared with that in the control group and Carboplatin group. Conclusion Hepatic injury was observed in the 3th day after injecting medicines ,the level of liver injury in Cisplatin group was heavier than that in Carboplatin group.