摘要
目的研究长春瑞滨在小鼠体内引起肝损害的时间及程度,并探讨其肝损伤作用机制。方法将小鼠分别尾静脉注射长春瑞滨5.6mg/kg及生理盐水,第1天给药,分别于给药第3,7,11,14天时测定各组小鼠血清生化指标、肝组织氧化及抗氧化指标,并检查肝组织病理学改变。结果试验组动物在给药第3天即出现肝细胞病理学改变,以肝细胞脂肪变性常见,50.00%为中等到大量脂肪变性,20.00%出现肝细胞坏死,以点状坏死多见,周围有炎性细胞,12.50%出现肝细胞瘀胆;血清丙氨酸氨基转移酶(ALT)较对照组无明显变化,天门冬酸氨基转移酶(AST)、碱性磷酸酶(ALP)、直接胆红素(DBIL)值较对照组明显升高;肝组织丙二醛(MDA)较对照组明显升高,还原型谷胱甘肽值则明显降低,超氧化物歧化酶(SOD)值与对照组比较无显著性差异。结论在无药物防护的情况下,长春瑞滨给药第3天即可引起肝组织损伤,多数为轻度,少数重度。
Objective To study the time and degree of liver injury in vivo induced by injecting vinorelbine in mice and its possible mechanism. Methods Mice were intravenously given vinorelbine at the dose of 5.6 mg/kg and normal saline by tail vein on 1 d. On 3, 7, 11, 14 d after injecting medicine, the serum biochemistry parameters, oxidation and antioxidation parameters of liver were detected and the histopathologic changes in hepatic tissues were observed. Results The pathologic changes of hepatocytes in the experiment group were found on 3 d after giving medicine, in which medium to large quantity of hepatocellular fatty degeneration accounted for 50. 00%;hepatocellular necrosis accounted for 20.00%, dominated by spotty necrosis with periphery inflammatory cells; hepatocellular cholestasis accounted for 12.50%. Serum alanine aminotransferase（ALT） in the experimental group had no obvious change, aspartate aminotransferase（AST）, alkaline phosphatase（ALP） and direct bilirubin（DBIL） were markedly increased compared with the control group. Malondialdehyde（MDA） of hepatic tissues in the experimental group was obviously higher than that of the control group, while reduced glutatbione was significantly reduced. Superoxide dismutase（SOD） had no obvious difference between the two groups. Conclusion In the condition of no medication protection, vinorelbine could cause the hepatocellular injury on 3d after drug administration, in which most is mild and minority is severe.
出处
《中国药业》
CAS
2010年第17期8-9,共2页
China Pharmaceuticals
基金
广西壮族自治区卫生厅计划课题
项目编号:Z2009170
关键词
长春瑞滨
肝损害
小鼠
vinorelbine
liver injury
mice
