新生大鼠高胆红素血症及脑病模型的建立与评价  

Establishment and evaluation of a hyperbilirubinemia and kernicterus model in neonatal rats

作　　者：王晓丽[1] 郭明星[1] 梁俊晖[1] 张常娥[1] 

机构地区：[1]广州医科大学病理生理学教研室,广东广州510182

出　　处：《中国病理生理杂志》2014年第8期1523-1531,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81170608);广东省自然科学基金博士启动资助项目(No.9451018201003604);广州市教育局基金资助项目(No.08A108)

摘　　要：目的：建立新生SD大鼠高胆红素血症和胆红素脑病模型并评价其效果。方法：将3日龄SD新生大鼠按窝系和体重随机均分为7组，分别经腹腔注射生理盐水（Con）以及胆红素6．25μg/g（T1）、12．5μg/g （T2）、25μg/g（T3）、50μg/g（T4）、100μg/g（T5）和200μg/g（T6），每天2次，共3 d。末次注射12 h后拍照、称重、取材，称量胃内容物重量，计算胃内容物指数和肝/体重比，测定血清总胆红素和游离胆红素浓度，检测脑组织的含水量、胆红素含量和ATP含量，HE和尼氏染色进行形态学检测。结果：随着注射次数和剂量的增加，新生鼠的一般表现逐渐变差，皮肤和黏膜黄染加重，活动次数逐渐减少，体重增长被抑制，T6组出现体重负增长；死亡率逐渐升高，T6组72 h死亡率接近100％，停止注射后观察1周，T4和T5组死亡率继续升高；与Con和T1组相比，T3～T5组胃内容物重量及其指数显著降低（P＜0．05）；T5组肝/体重比显著升高（P＜0．05）；血清总胆红素、游离胆红素和脑组织总胆红素的浓度在T1～T5组逐渐递增；各组大鼠脑组织的含水量没有差异；脑组织ATP含量在T1～T5组先升高后降低，T3组达高峰，与Con 组相比，T4组和T5组显著降低（ P＜0．05）。 HE染色结果显示：随着胆红素浓度升高，各组大鼠大脑皮层神经元数量逐渐减少，T4和T5组神经元结构紊乱，细胞肿胀，部分细胞核染色质致密浓缩。尼氏染色显示，随着胆红素浓度增多，神经元胞体逐渐变小，尼氏小体减少、染色逐渐变浅， T4和T5组部分神经元溶解甚至消失。结论：新生3日龄SD大鼠腹腔注射胆红素12．5、25、50和100μg/g，每天2次，注射3 d可致高胆红素血症，50和100μg/g可引起胆红素脑病的发生。AIM：ToestablishandevaluateahyperbilirubinemiaandkernicterusmodelinneonatalSDrats. METHODS：Three-day-old SD rats were randomly divided to 7 experimental groups by litter and body weight , and were in-traperitoneally injected with physiological saline （control group）, and 6.25μg/g （T1）, 12.5μg/g （T2）, 25μg/g （T3）, 50μg/g （T4）, 100μg/g （T5） and 200μg/g （T6） bilirubin, respectively, twice every day for 3 d.All rats were photo-graphed , weighed and killed 12 h after the last injection .The contents of the stomach were drawn and weighed , and the index was calculated .The liver/body weight ratio was determined , the total and unconjugated bilirubin in the serum and total bili-rubin in the brain were calculated , and the contents of ATP and water in the brain were measured .HE and Nissl staining were used to observe the pathological changes .RESULTS：Along with the increase in bilirubin , gradual exacerbation of the general performance of the rats , and yellowish discoloration of the skin and mucous membranes were observed .The degree of the activity gradually reduced , and the weight gain was suppressed .The weight of T6 group showed negative growth , and the 72 h mortality rate was close to 100%.The mortality rate in T4 and T5 groups continued to rise 1 week after injection .Com-pared with control group , the weight of stomach contents and stomach content index in T 3~T5 groups significantly decreased （P＆lt;0.01）.The liver/body weight ratio in T5 group was significantly higher （P＆lt;0.05）.The concentrations of serum total and unconjugated bilirubin and brain bilirubin levels in T 1~T5 groups were gradually increased , while the brain water con-tent had no difference among groups .The brain ATP content in T1~T5 groups increased at the beginning and reached its＆amp;nbsp;peak in T3 group, but compared with control group , that in T4 group and T5 group significantly reduced （P＆lt;0.05）.HE re-sults showed that , with the increase in bilirubin concentration , the nu

关 键 词：胆红素 高胆红素血症 核黄疸 大鼠 模型 动物 

分 类 号：R363[医药卫生—病理学]