期刊文献+

髓过氧化物酶与大剂量顺铂所致小鼠肝功能变化关系的探讨

Relation between Peroxidase and acute liver injury induced by high-dose cisplatin in mice
原文传递
导出
摘要 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 explore the changes of peroxidase in liver injury induced by high-dose Cisplatin(DDP) in mice.Method C57BL/6 mice were randomly divided into DDP group and control group according to body weight.Single dose of DDP(15 mg/kg) was injected intraperitoneally,and the same volume of natural saline(NS) was given as control.Blood samples were obtained from mice(10 per group) before and 6 h,12 h,24 h,48 h after DDP administration.Blood urea nitrogen(BUN),creatinine(Cre) and alanine aminotransferase(ALT) were measured.Liver index was calculated and the morphological changes in liver tissue were observed by light microscopy.The levels of peroxidase(MPO) in blood and 10% liver tissue homogenate were determined by colorimetry.Result The mice suffered acute renal failure at 48 h after DDP administration.Plasma ALT contents increased significantly 6 hours after DDP administration(P0.05) and sustained at a high level subsequently.The liver index of mice increased significantly after DDP administration(P0.01).Widespread hydropic degeneration of hepatocytes and spotty necrosis in hepatic lobules with inflammatory cell infiltration were seen in the liver of mice after DDP administration.The MPO contents in 10% liver tissue homogenate increased to(1.54±0.45)U/g at 6 h after DDP administration,significantly higher than that in control group(0.58±0.28)U/g(P0.01).It decreased to normal level subsequently.The blood MPO levels increased gradually and reached to its high level at 48 h after DDP administration(12.78±2.78)U/L,significantly higher than that in control group(8.06±1.89)U/L(P0.05).Conclusion High-dose DDP can induce acute liver injury in mice,which may be related to the activation of neutrophils and the release of MPO in liver.
出处 《中国微生态学杂志》 CAS CSCD 2012年第4期314-317,共4页 Chinese Journal of Microecology
基金 大连市科技计划项目基金资助项目(2009E12SF165)
关键词 大剂量顺铂 急性肝损伤 髓过氧化物酶 C57BL/6小鼠 High-dose Cisplatin Acute liver injury Peroxidase C57BL/6 mice
  • 引文网络
  • 相关文献

参考文献4

二级参考文献37

  • 1王黎,裴瑞,杨红梅,陈洁,桂兴芬.顺铂诱导肾损伤过程中肾皮质脂质过氧化的变化[J].中国应用生理学杂志,2004,20(4):393-395. 被引量:20
  • 2石凡华,梁瑞兰,高慧英,杜玉清.顺铂剂量与肾功能损伤相关性的实验观察[J].潍坊医学院学报,2005,27(4):262-263. 被引量:8
  • 3张建青,赵文安,刘霏,于子涵,杜宣,刘艳华,王晓倩,张锦程,滕忠义,刘星,姜妙娜,李墨林.一氧化氮在大剂量顺铂所致大鼠肾损伤早期中的变化[J].大连医科大学学报,2006,28(5):381-383. 被引量:9
  • 4SORDILLO P P,MAGILL G B,BRENNER J,et al. Cisplatin a phase Ⅱ evaluation in previously untreated patients with soft tissue sarcoma[ J ]. Cancer, 1987,59(5) :884-886. 被引量:1
  • 5ZHANG J G,ZHONG L F,ZHANG M,et al. Protection effects of procaine on oxidative stress and toxictities of renal cortical slices from rats caused by cisplatin in vitro[J]. Arch Toxicol,1992,66(5) :354-358. 被引量:1
  • 6王思理.细菌内毒素检查法一定量法(全国培训班教材)[M].中国药品生物制品检定所,天津市药检所,天津大学无线电厂联合印制,1998:115-158. 被引量:1
  • 7JO S K,CHA D R,CHO W Y,et al. Inflammatory cytokines and lipopolysaccharide induce Fas-mediated apoptosis in renal tubular cells [J]. Nephron,2002,91 (3) :406-415. 被引量:1
  • 8Yao X,Panichpisal K, Kurtzman N, et al. Cisplatin nephrotoxicity: a review[J]. Am J Med Sci,2007,334(2) :115 - 124. 被引量:1
  • 9Mayeux PR. Pathobiology of lipopolysaccharide [ J ]. J Toxicol Environ Health, 1997,51 ( 5 ) : 415 - 435. 被引量:1
  • 10[1]Witko-Sarsat V,Rieu P,Descamps-Latscha B,et al.Neutrophils:molecules,functions and pathophysiological aspects[J].Lab Invest,2000,80:617-653. 被引量:1

共引文献46

相关主题

;
使用帮助 返回顶部