Protective Effects Of Yinzhihuang Injection On Bilirubin-induced Brain Injury In Neonatal Rat

Aim:The bilirubin concentrations, the Na+-K+-ATPase activities, the morphologicalstructures and the ultrastructures of the brain tissues had be observed in the neonatal rat withbilirubin-induced brain injury after treatment of Yinzhihuang injection to explore theprotective effects of it on bilirubin-induced brain injury and further understand themechanisms of the bilirubin-induced brain injury.Methods:One hundred and seventy-five seven-day old neonatal rats had been randomly dividedinto normal control group, brain injury group, therapy groupⅠ, therapy group Ⅱandtherapy group Ⅲ. Bilirubin solutions of120mg·kg-1mass fraction were injected into theabdominal cavity of seven-day old rats for inducing brain injury. Meanwhile, Yinzhihuanginjection solutions of513.2mg·kg-1,265.5mg·kg-1and132.8mg·kg-1mass fraction wereinjected into the abdominal cavity of the neonatal rats each day for treatment of the braininjury during two weeks in therapy groupⅠ, therapy group Ⅱand therapy group Ⅲrespectively. After48hours and2weeks treatment, the bilirubin concentrations of the braintissues were examined via a diazo method, the Na+-K+-ATPase activities of the brain tissueswere analyzed by rooting phosphorus, the morphological structures of hippocampus tissuewere observed via light microscope with Hematoxylin-Eosin (HE) staining and theultrastructures of the hippocampal neurons were observed via transmission electronmicroscope in the rats.Results:1.After48h and2weeks treatment, the bilirubin concentrations of the brain tissues in therats of brain injury group and three therapy groups were significantly higher than that of normal control group (P <0.01). But the bilirubin concentrations of the brain tissues in therats of therapy group Ⅰ and therapy group Ⅱ were significantly lower than that ofinjury group (P <0.05) after48hours treatment, and the bilirubin concentrations of thebrain tissues in the rats of three therapy groups were significantly lower than that ofinjury group (P <0.05) after2weeks treatmen，which was characterized by significantdosage-effect relationship.2.After48h and2weeks treatment, the Na+-K+-ATPase activity of the brain tissues in therats of brain injury group and three therapy groups were significantly lower than that ofnormal control group (P <0.01). But the Na+-K+-ATPase activity of the brain tissues inthe rats of three therapy groups were significantly higher than that of brain injury group(P <0.05), which was characterized by significant dosage-effect relationship.3.After48h and2weeks treatment, the derangement, rarefaction, body shrinkage,karyopyknosis and cytoplasm cavitation of the neurons were found under light microscope,and the swelling, deformities, blurred innner and outer membrane and broken crista of themitochondria and the swelling, deformities and decreased ribosome attachment of therough endoplasmic reticulum were observed under transmission electron microscope in CA1region of hippocampus in the rats of brain injury group. The above abnormal changes wereimproved in the rats of three therapy groups.Conclusion:1.Yinzhihuang injection has a protective effect on bilirubin-induced brain injury in neonatalrats, which was characterized by significant dosage-effect relationship.2.Protection of Na+-K+-ATPase activity and mitochondria of the neurons may be theimportant mechanisms responsible for the action of Yinzhihuang injection onbilirubin-induced brain injury.