溶血致新生大鼠高胆红素血症动物模型的建立及评价

Establishment and evaluation of a neonatal rat model of hyperbilirubinemia caused by hemolysis

目的探讨建立操作简便可行、成功率高、具有良好模拟性的新生大鼠高胆红素血症动物型,为开展高胆红素血症致核黄疸及相关神经损伤机制研究提供实验基础模型。方法随机选取7日龄SD大鼠,分别采用25、50、75 mg/kg三个梯度腹腔内注射盐酸苯肼,建立溶血致高胆红素血症动物模型,同时设立对照组,分别在实验处理48h后,测定血、脑组织胆红素、同时进行脑组织NSE分析对模型进行评价。结果三组实验组分别与对照组相比,血、脑组织胆红素、脑组织NSE均大于对照组,差异具有显著性(P<0.05),而血红蛋白含量小于对照组,差异具有显著性(P<0.05);50 mg和75 mg剂量组血、脑组织胆红素、脑组织神经元特异性烯醇化酶(NSE)均大于25 mg剂量组,而血红蛋白含量小于25 mg剂量组,差异具有显著性(P<0.05);50 mg和75 mg剂量组间相比各项指标差异无显著性(P>0.05)。结论腹腔注射盐酸苯肼能够制作出符合临床特征的高胆红素动物模型,50 mg/kg为最佳浓度,是建立新生儿高胆红素血症动物模型的理想方法。

Objective To establish and evaluate a reliable and highly reproducible neonatal rat model of hyperbilirubinemia and to provide an experimental basis for research of kernicterus and related mechanism of neuroinjury. Methods Sixty 7-day old SD rats（ 28 male and 32 female） were used in this study. Three doses of phenylhydrazine hydrochloride（ 25,50,and 75 mg / kg） were intraperitoneally injected respectively to the neonatal rats to establish models of hyperbilirubinemia induced by hemolysis. The control group was set up at the same time. 48 hours after the experimental treatment,the bilirubin in blood and brain tissue,neuron-specific enolase（ NSE） of brain tissue,and hemoglobin were detected to evaluate the models. Results Compared with the control group,the bilirubin in the blood and brain tissue and the brain tissue NSE in the three experimental groups were significantly higher than that in the control group（ P〈0. 05）,while hemoglobin content was significantly lower than that in the control group（ P〈0. 05）. The bilirubin of blood and brain tissue and brain tissue NSE in the 50 mg / kg and 75 mg / kg dose phenylhydrazine hydrochloride groups were significantly higher than that of the 25 mg / kg dose group（ P〈0. 05）,while hemoglobin content was significantly lower than that of the 25 mg / kg dose group（ P〈0. 05）. There were no significant differences between the 50 mg and 75 mg dose groups（ P〉0. 05）. Conclusions Intraperitoneal injection of phenylhydrazine hydrochloride can be used to produce neonatal rat models of hyperbilirubinemia,mimicking the clinical features of this disease,and 50 mg / kg of phenylhydrazine hydrochloride isthe best concentration. It is an ideal method to establish newborn rat models of hyperbilirubinemia.