Effect Of NGF On Fas And Fas-Ligand Expression In Brain Tissue Of Neonatal Rats With Hyperbilirubinemia

Objective:Hyperbilirubinemia of newborn is one of the common pathological states of the neonatal period, severe cases can be complicated with bilirubin encephalopathy, even irreversible brain injury(BI). This experiment has set up the high bilirubin newborn rat model, to observe the change of Fas/Fas-L of brain tissue after the modules ware made the nerve growth factor(NGF), to explore the pathogenesis of high bilirubin blood disease and possible mechanisms of cerebral protective effect of NGF, to provide a theoretical basis for clinical drug treatment of hyperbilirubinemia, further, in order to reduce the mortality of bilirubin encephalopathy.Methods:To select 120 SD rats 7 days of age, they were randomly divided into hyperbilirubinemia model group(Group A, n = 40), NGF intervention group(Group B, n = 40),and normal control group respectively( Group C, n = 40). When the modules were set up,each experimental group was divided into five sub-groups based on different time points(n=8):6h, 12 h, 24 h, 48 h, 72 h. When the rat models were set up successful, the rats of group B were injected intraperitoneally 50μg/KG/d of NGF at once, which need to be conducted in three consecutive days, and the brain tissue of rats in each experimental group were taken at different time points. Fas/Fas- L were observed and measured by HE staining and immune histochemical methods. Then calculate the results and analyze the statistic to get the conclusion.Results:(1) Observation of animal behavior: The rats of A、B two groups showed abnormal behavior after set up the model, but the rats in group C were not founded abnormal behavior.(2) The appearance of brain tissue: After set up the model with founded the degrees of edema, atrophy, necrosis and liquefaction in group A.The degree of brain tissue injury were lighter compared the group A with group B.The group C were normal appearance.(3)HE staining: The rat brain tissue appeared various degrees of nerve cell swelling and degeneration in A 、 B groups after modeling 6h~12h, or necrosis after modeling 24h~48h, nuclear shrinkage and fragmentation in the lesion center after modeling 72 h. All the degree of damage above were lower in group B compared with group A. All the brain cells ingroup C were normal.(4)Expressions of Fas/ Fas-L:Fas/Fas-L positive cells increased gradually in brain tissue in group A and group B after set up the model, Fas/Fas-L expression decreased significantly of the brain tissue in group B under NGF intervention, and each time point were lower than group A, but still higher than group C(P < 0.05). Each time point of group C had only a little expression in Fas/Fas- L, there was no statistically significant difference at each time point compared within the group(P > 0.05).Conclusions:(1) Observation of animal behavior has changed when the rate models have set up,confirmed the rate models with hyperbilirubinemia were successed;(2) Different degrees of edema atrophy and liquefaction necrosis occurs in brain tissue after when the rate models were set up, which abated after NGF treatment,the perspective of pathology verified hyperbilirubinemia caused by nerve damage can reduce the NGF treatment;(3)The expression of Fas / Fas-L were down-regulating by NGF, preventing the process of brain injury, in which the intervention 48 ~ 72 h when the most obvious effect.