An Experimental Study On The Relationship Of Hyperbilirubinemia And Neuroncyte Apoptosis

Objective To explore the expression of Fas pretein, N-methyl-D-aspartate(NMDA) receptor, the rate of neuronal apoptosis in the hippocampus under the hyperbilirubinemia and elucidate the molecular mechanism of bilirubin neurotoxicity. Methods The anminals were radominzed into 3 groups: control group(CG), test-1 group(TiG)and test-2 group(T2G). Bilirubin were injected into 7-day old Sprague-Dawley rats' abdominal cavity to set up the hyperbilirubinemia model.Oberving their neuronal behaviours and the pathological changes, investgating the bilirubin content inplasma and brain. The expression of Fas protein, NMDA receptors, the rate of neuronal apoptosis were investigated with immunohistochemical methods and flow cytometry in the hippocampus and the correlations among them were explored. Results (1) The neurons and mitochondria swollen, mitochondria spines reduced in T1G, neurons had acidophile degeneration , chronmate in nucleouses concentrated nucleus pores appeared in T2G . These changes accorded with pathological changes of cell apoptosis . (2) The level of plasm bilirubin in TiG and TaG were higher than that of CG , there were significant difference among them . (3) The expression of NMDA receptors were in neurons mainly , the expression of Fas protein were in neurons and ganlics.There was a positive correlation among the expression of NMDA receptors, Fas protein , the rate of neuronal apoptosis and the level of neuronal bilirubin (r> 0.6) . There was obvious difference among CG, T1G and T2G (P<0.01) . (4) The rates of neurons apoptosis had significant differenceamong CG , T1G , T2G .Conclusion The bilirubin neurotoxicity is mediated by the NMDA receptors activity increased and Fas system, with which induced neuronal apoptosis.