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目的利用大剂量顺铂(Cisplatin,DDP)诱发小鼠急性肾功能衰竭的动物模型,了解大剂量DDP在引起肾损伤的同时对小鼠肝的毒性作用,探讨髓过氧化物酶(Peroxidase,MPO)与DDP所致小鼠肝功能变化的关系。方法 C57BL/6小鼠50只,雌雄各半,依体重随机分为DDP用药组和生理盐水(NS)对照组。15 mg/kg DDP单次腹腔内注射,等量NS对照。分别取对照组小鼠和DDP用药后6、12、24和48 h小鼠各10只,称重后乙醚麻醉,内眦静脉取血检测肝、肾功能;剖腹取肝、称重、计算肝系数,并取少量肝组织行HE染色、形态学观察;检测血浆和肝组织匀浆中MPO活性,统计学分析。结果大剂量DDP用药后48 h,小鼠出现急性肾功能衰竭。DDP用药后6 h血清谷丙转氨酶(ALT)含量达(91.0±11.3)IU/L,与对照组比较差异有统计学意义(P<0.05),随后血清ALT含量持续维持在高水平。DDP用药后各组小鼠肝系数明显升高,光镜下见肝细胞广泛变性水肿,肝小叶中可见点状坏死及炎细胞浸润。DDP用药后6 h,小鼠肝组织匀浆MPO含量显著升高,达(1.54±0.45)U/g,与对照组(0.58±0.28)U/g差异有统计学意义(P<0.01),随后MPO含量降至正常水平;DDP用药后小鼠外周血MPO含量缓慢增高,用药后48 h达(12.78±2.78)U/L,与对照组(8.06±1.89)U/L比较差异有统计学意义(P<0.05)。结论大剂量DDP在诱发小鼠急性肾功能衰竭的同时还可引起小鼠急性肝细胞的破坏,其发生可能与肝组织内白细胞的激活及MPO的释放有关。
OBJECTIVE: To investigate the toxic effects of high dose DDP on liver injury induced by renal injury in mice induced by Cisplatin (DDP) and to investigate the effect of peroxidase (MPO) ) And DDP-induced liver function changes in mice. Methods Fifty C57BL / 6 mice, male and female, were randomly divided into two groups according to body weight: DDP treatment group and NS control group. 15 mg / kg DDP single intraperitoneal injection, the same amount of NS control. The mice in control group and DDP group were given 10, 6, 12, 24 and 48 h after DDP treatment respectively. The rats were weighed, Coefficient, and take a small amount of liver tissue HE staining, morphological observation; detection of plasma and liver homogenate MPO activity, statistical analysis. Results After 48 hours of high-dose DDP, mice developed acute renal failure. Serum alanine aminotransferase (ALT) level reached 91.0 ± 11.3 IU / L at 6 h after DDP treatment, which was significantly different from that of the control group (P <0.05). Subsequently, serum ALT level was maintained at a high level. After DDP treatment, the hepatic coefficient of mice in each group was significantly increased, and the hepatocytes were widely degenerated and edematous under light microscope. The punctate necrosis and inflammatory cell infiltration were seen in the hepatic lobules. At 6 h after DDP treatment, the MPO content in liver homogenate increased significantly (1.54 ± 0.45) U / g, which was significantly lower than that in control group (0.58 ± 0.28) U / g (P <0.01) The content of MPO decreased to the normal level. The MPO level in peripheral blood of DDP group increased slowly and reached the peak at 12 h (12.78 ± 2.78) U / L at 48 h after drug administration, which was significantly lower than that of control group (8.06 ± 1.89) U / L Significance (P <0.05). Conclusion High-dose DDP can induce the acute renal failure in mice as well as induce the destruction of acute hepatocytes in mice, which may be related to the activation of white blood cells and the release of MPO in liver tissues.