ABSTRACT
[ABSTRACT]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<0.01).The liver/body weight ratio in T5 group was significantly higher (P<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 peak in T3 group, but compared with control group , that in T4 group and T5 group significantly reduced (P<0.05).HE re-sults showed that , with the increase in bilirubin concentration , the number of the neurons in the cerebral cortex of the rats de-creased.In T4 group and T5 group, the neuronal structural disorder , cell swelling, nuclear pyknosis, fragmentation and dis-solution, increase in non-homogeneous structure of the material dyed red , and disappearance of nuclear staining were ob-served.Nissl staining showed that , compared with control group , in T1 group and T2 group, the cortical neurons became smaller, Nissl bodies decreased , and cytoplasmic staining changed little .The cortical neuronal tigroid body color became light gradually, neuron cells become small , and Nissl bodies decreased obviously in T 3, T4 and T5 groups.The T4 and T5 rat ce-rebral cortical neurons dissolved or even disappeared .CONCLUSION:Newborn 3-day-old SD rats receiving intraperitoneal injection of bilirubin at doses of 12.5, 25, 50 and 100μg/g, 2 times a day, can induce hyperbilirubinemia , and 50 and 100μg/g can cause bilirubin encephalopathy .