BDNF及高亲和力受体TrKB在胆红素神经损伤豚鼠皮层及海马表达变化的实验研究

Experimental research on expression changes of BDNF and high affinity receptor TrKB in cerebral cortex and hippocampus of guinea pigs with bilirubin induced nerve injury

目的:探讨新生豚鼠胆红素脑神经损伤元时脑源性神经营养因子(BDNF)及受体酪氨酸激酶B(TrKB)在大脑皮质及海马表达特点。方法:取生后2～5天内的豚鼠60只,随机分为3组,C组、T1组、T2组。C组为对照组;T1组:腹腔注射晶体胆红素100μg/g;T2组腹腔注射胆红素200μg/g,分别在4h、8h处死。做脑组织切片,电镜,光镜观察病理改变,并采用免疫组化和图像分析,观察不同时间点BDNF、TrKB在皮层及海马表达变化。结果:①胆红素脑神经元损伤模型成功建立。②T14h、T24h在早期皮层及海马是降低的。随时间延长,BDNF表达明显上升,T14h、T24h与C4h比较,P<0.05,T14h、T24h与T18h、T28h比较,P<0.05。③TrKB在皮层和海马表达是随时间延长和损伤加重表达增加,T14h、T18h、T24h、T28h与C4h、C8h比较,P<0.05。结论:胆红素脑神经元损伤中,皮层和海马BDNF、TrKB升高可能减轻神经元损伤,在抑制神经元凋亡和神经元修复中发挥重要作用,有利神经元修复和再生,可能是胆红素脑神经元损伤时机体的自我保护机制之一。

Objective：To explore the expression characteristics of brain derived neurotrophic factor （BDNF） and Tyrosine kinase B （TrKB） in cerebral cortex and hippocampus of guinea pigs with bilirubin induced nerve injury.Methods：60 guinea pigs of 2～5 days after birth were selected and divided into 3 groups randomly：C group,T1 group and T2 group.C group was control group;the guinea pigs in T1 group were treated with intraperitoneal injection of crystal bilirubin 100 μg/g;the guinea pigs in T2 group were treated with intraperitoneal injection of bilirubin 200 μg/g,then they were sacrificed at 4 hours and 8 hours after intraperitoneal injection,brain tissue slice technique was used in the study,and electron microscope and light microscope were used to observe the pathological changes;the changes of BDNF and TrKB expressions in cerebral cortex and hippocampus at different time points were observed by immunohistochemical method and image analysis.Results：The models of bilirubin induced neuron injury were established successfully;at 4 hours after intraperitoneal injection,the expression levels of BDNF and TrKB in T1 group and T2 group decreased,the expression level of BDNF increased with time,there was significant difference among C group,T1 group and T2 group （P0.05）,and there was significant difference at 4 hours and 8 hours after intraperitoneal injection between T1 group and T2 group （P0.05）,the expression level of TrKB in cerebral cortex and hippocampus increased with time and aggravation of the disease,there was significant difference at 4 hours and 8 hours after intraperitoneal injection between T1 group and T2 group （P0.05）.Conclusion：The increases of BDNF and TrKB in cerebral cortex and hippocampus may relieve neuronal injury,play important roles in inhibiting apoptosis of neuron and promoting neuron repairment,which is beneficial to neuron repairment and regeneration,and the phenomenon may be a self-protective mechanism of bilirubin induced neuron injury.