高胆红素血症及胆红素脑病新生大鼠模型的建立与评价

Establishment and Evaluation of Neonatal Rat Model with Hyperbilirubinemia and Bilirubin Encephalopathy

目的为新生儿黄疸的发病机制及诊疗建立可靠的动物模型。方法随机将30只7 d龄SD大鼠分为5组:腹腔注射生理盐水组(T0组)、腹腔注射50 mg/kg胆红素组(T1组)、腹腔注射100 mg/kg胆红素组(T2组)、腹腔注射150 mg/kg胆红素组(T3组)、腹腔注射200 mg/kg胆红素组(T4组),并于24 h后取材。结果随着胆红素注射剂量的增加,实验大鼠皮肤黏膜黄染加重,活动次数减少;血清及脑组织胆红素递增,与T0组比较差异均有统计学意义(P<0.05);血清S-100β递增,与T0组比较差异均有统计学意义(P<0.05),T1组与T2组血清S-100β水平比较差异无统计学意义(P>0.05);神经细胞的凋亡率递增,与T0组比较差异均有统计学意义(P<0.05),T3组与T4组比较差异无统计学意义(P>0.05);HE染色示海马组织神经元数量减少,结构紊乱,细胞肿胀、变形。结论腹腔注射胆红素能制作高胆红素血症模型,腹腔注射100 mg/kg胆红素和150 mg/kg胆红素可建立胆红素脑病的模型,腹腔注射150 mg/kg胆红素适合胶质细胞损伤的研究。

Objective To establish the reliable animal model for the pathogenesis and diagnosis of neonatal jaundice.Methods Thirty 7-day-old Sprague-Dawley（ SD） rats were randomly divided into 5 groups： intraperitoneal injection of normal saline group（ group T0）,intraperitoneal injection of 50 mg/kg bilirubin group（ group T1）,and intraperitoneal injection of 100 mg/kg bilirubin group（ group T2）,intraperitoneal injection of 150 mg/kg bilirubin group（ group T3）,intraperitoneal injection of 200 mg/kg bilirubin group（ group T4）.Serum were taken after24 hours.Results With the increase of the dose of bilirubin,the jaundice of the skin and mucosa were aggravated,and the number of activities were decreased in rats.Compared with group T0,the levels of bilirubin and S-100 β protein in serum and brain tissue increased in group T1,group T2,group T3 and group T4（ P〈0.05）.There was no significant difference in serum S-100 β protein levels between group T1 and group T2（ P〈0.05）.The apoptotic rate of nerve cells increased compared with group T0（ P〈0.05）.There was no significant difference between group T3 and group T4（ P 0. 05）. Hematoxylin-Eosin（ HE） staining showed that the number of neurons in hippocampus was reduced,the structure was disordered,and the cells were swollen and deformed.Conclusion The model of hyperbilirubinemia is established by intraperitoneal injection of bilirubin.The model of bilirubin encephalopathy is established by intraperitoneal injection of 100 mg/kg and 150 mg/kg bilirubin.Intraperitoneal injection of 150 mg/kg bilirubin is suitable for glial cell injury research.