目的 建立新生猪溶血性黄疸动物模型,以进一步研究新生儿溶血性黄疸的病理生理。方法 7日龄纯种大约克白猪分成实验组和对照组,每组各6只。并采用免疫新西兰大白兔的方法 制备兔抗猪红细胞抗体,分离兔抗猪红细胞血清。实验组静脉注射兔抗猪红细胞血清5mL,对照组注射5mL生理盐水。两组均每6h采血送检血常规及肝功能。结果 实验组注射兔抗猪红细胞血清18h后血清胆红素水平高于对照组(64±30μmol/Lvs20±4μmol/L,P<0.05),48h达高峰(275±31μmol/L),96h明显降低(95±17μmol/L),均高于对照组(P<0.05)。注射抗血清后18h,实验组红细胞降至(4.58±0.32)×1012/L,低于对照组[(5.09±0.44)×1012/L](P<0.05);24h实验组红细胞[(4.21±0.24)×1012/L]和HB(87±3g)进一步降低,低于对照组[(5.11±0.39)×1012/L,97±6g](P<0.05);二组间的红细胞、血红蛋白差异在36~48h达高峰。结论 新生猪溶血性黄疸模型较好地模拟了人类溶血性黄疸的病理过程,为更进一步研究新生儿溶血病提供了良好的生物物质基础。
Abstract
Objective To establish a neonatal pig model of hemolytic jaundice. Methods Twelve sevenday-old purebred Yorkshire pigs were randomly divided into an experimental group and a control group (n=6 each). Immunization of New Zealand white rabbits was used to prepare rabbit anti-porcine red blood cell antibodies, and rabbit anti-porcine red blood cell serum was separated. The neonatal pigs in the experimental group were given an intravenous injection of rabbit anti-porcine red blood cell serum (5 mL), and those in the control group were given an intravenous injection of normal saline (5 mL). Venous blood samples were collected every 6 hours for routine blood test and liver function evaluation. Results The experimental group had a significantly higher serum bilirubin level than the control group at 18 hours after the injection of rabbit anti-porcine red blood cell serum (64±30 μmol/L vs 20±4 μmol/L; P<0.05). In the experimental group, the serum bilirubin level reached the peak at 48 hours (275±31 μmol/L), and decreased significantly at 96 hours after the injection (95±17 μmol/L), but all significantly higher than that in the control group (P<0.05). At 18 hours after the injection, the experimental group had a significantly lower red blood cell (RBC) count than the control group [(4.58±0.32)×1012/L vs (5.09±0.44)×1012/L; P<0.05]; at 24 hours, the experimental group showed further reductions in RBC count and hemoglobin level and had significantly lower RBC count and hemoglobin level than the control group [RBC: (4.21±0.24)×1012/L vs (5.11±0.39)×1012/L, P<0.05; hemoglobin: 87±3 g vs 97±6 g, P<0.05]. The differences in RBC count and hemoglobin level between the two groups were largest at 36-48 hours. Conclusions The neonatal pig model of hemolytic jaundice simulates the pathological process of human hemolytic jaundice well and provides good biological and material bases for further investigation of neonatal hemolysis.
关键词
新生儿溶血病 /
高胆红素血症 /
动物模型 /
猪
Key words
Neonatal hemolysis /
Hyperbilirubinemia /
Animal model /
Pigs
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参考文献
[1] Rennie J, Burman-Roy S, Murpy S. Neonatal jaundice: summary of NICE guidance[J]. BMJ, 2010, 340: c2409.
[2] 吴仕孝. 新生儿溶血病的研究进展[J]. 中国实用儿科杂志, 1999, 14(2): 72-74.
[3] Altuntas N, Yenicesu I, Himmetoglu O, et al. The risk assessment study for hemolytic disease of the fetus and newborn in a university hospital in Turkey[J]. Transfus Apher Sci, 2013, 48(3): 377-380.
[4] Markham KB, Rossi KQ, Nagaraja HN, et al. Hemolytic disease of the fetus and newborn due to multiple maternal antibodies[J]. Am J Obstet Gynecol, 2015, 213(1): 68.e1.
[5] 裴进升, 张华. 胆红素神经毒性机制及早期监测的研究进展
[J]. 华夏医学, 2011, 24(5): 619-622.
[6] 陈敏, 陈昌辉, 刘会领, 等. 胆红素对新生儿脐血单核细胞 NF-κB 表达的影响[J]. 中华临床医师杂志(电子版), 2012, 6(3): 635-638.
[7] Sabreen S, Khan MR, Khan RA. Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat[J]. BMC Complement Altern Med, 2011, 11: 48.
[8] 朱强, 王科, 钱晓锋, 等. 改良小鼠酒精性肝损伤模型的建立[J]. 中华临床医师杂志(电子版), 2010, 4(9): 1532-1536.
[9] van Swelm RPL, Laarakkers CM, van der Kuur EC,et a1. Identification of novel translational urinary biomarkers for acetaminophen induced acute liver injury using proteomic profiling in mice[J]. PLoS One,2012,7(11):e49524.
[10] Luyendyk JP, Flanagan KC, Wtliams CD, et al. Tissue factor contributes to neutrophil CD11b expression in alphanaphthylisothiocyanate-treated mice[J]. Toxicol Appl Pharmol, 2011, 250(3): 256-262.
[11] 欧巧群, 钱新华, 黄笑群, 等. ANIT 诱导大鼠亚急性肝内胆汁淤积的生化和病理变化[J]. 胃肠病学和肝病学杂志, 2015, 24(4): 463-465.
[12] 张春兴, 王芳, 廖彩仙, 等. 梗阻型黄疸小鼠模型构建及相关指标观察[J]. 大连医科大学学报, 2014, 36(1): 23-26.
[13] Sun XM, Kang P, Tao K. Causes of immune dysfunction in hyperbilirubinemia model rats[J]. Asian Pac J Trop Med, 2015, 8(5): 382-385.
[14] 詹影影. ABO 血型系统诊断新生儿溶血病的实验研究[J]. 中国卫生检验杂志, 2010, 20(6): 1421-1422.
[15] 陈玫, 毕晓琳, 叶萍, 等. 孕妇血清中抗-A(B)IgG 亚类与新生儿溶血病关系的研究[J]. 中国输血杂志, 2005, 18(6): 484-486.
[16] 包亚双, 吴树林, 张红艳, 等. 关于新生仔猪溶血症防治探讨[J]. 畜禽业, 2013, 5: 84.
[17] 金龙, 蒋智, 夏渝东, 等. 猪不同年龄段骨骼肌的甲基化组比较分析[C]. 四川省畜牧兽医学会2014 学术年会论文集. 成都: 四川省畜牧兽医学会, 2014: 33-43.
[18] 张世昌, 王英杰, 陈志, 等. 乳猪肝细胞的生物学特性观察[J]. 第三军医大学学报, 2007, 29(24): 2307-2310.
[19] 朴梅花, 王庆红. 新生儿黄疸的治疗[M]// 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学. 第4 版. 北京: 人民卫生出版社, 2011: 300-306.
[20] 李波. 血液灌流治疗新生儿重症高胆红素血症19 例疗效及安全性观察[J]. 实用医院临床杂志, 2011, 8(5): 145-147.
基金
苏州市科技发展计划项目(社会发展-应用基础研究SYSD2010139)。
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