摘要目的 研究脑源性神经营养因子(BDNF)通路在功夫菊酯(LCT)干扰雌激素(E2)的促海马神经细胞PSD95表达中的作用.方法 以培养小鼠海马神经细胞系HT22细胞为模型,分组如下:LCT(50 μmol/L)、E2(17β-Estradiol,E2)(10 nmol/L)、LCT(50 μmol/L)+BDNF信号通路的抑制剂(TrkB FC,20μg/ml)、E2(10 nmol/L)+TrkB FC(20 μg/ml)、LCT(50 μmol/L)+ERα抑制剂(ICI182 780,1μmol/L)、E2(10nmol/L)+ ICI182 780(1 μmol/L)、LCT(50 μmol/L)+ E2(10 nmol/L),处理24 h,噻唑蓝(MTT)法检测细胞活性,免疫蛋白印迹法检测PSD95蛋白表达,ELISA法检测培养上清和BDNF水平.结果 与溶剂对照组比较,LCT组和E2组的PSD95蛋白以及BDNF蛋白基因水平均明显增加,差异有统计学意义(P＜0.05);与LCT组比较,LCT+TrkB FC组的PSD95蛋白水平明显降低,LCT+ICI组的BDNF蛋白和基因水平明显降低,差异有统计学意义(P＜0.05);与E2组比较,E2+TrkB FC组的PSD95蛋白水平明显降低,E2+ICI组的BDNF蛋白和基因水平明显降低,差异有统计学意义(P＜0.05);与E2组相比较,LCT+E2组的PSD95蛋白水平以及BDNF蛋白和基因水平均明显降低,差异有统计学意义(P＜0.05).结论 E2通过BDNF通路促进神经细胞PSD95表达,虽然LCT单独作用有类似E2的效应,但LCT可通过干扰BDNF通路抑制E2对海马神经细胞PSD95表达的促进作用.

abstractsObjective To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons.Methods HT22 cell line were used to,treating with lambda-cyhalothrin (LCT,50 μmol/L),17 β-Estradiol (E2,10 nmol/L),LCT (50 μmol/L) +TrkB FC (20 μg/ml),E2 (10 nmol/L) +TrkB FC (20 μg/ml),LCT(50 μmol/L) +ICI182 780 (1 μmol/L),E2 (10 nmol/L)+ ICI182 780 (1 μmol/L),LCT (50 μmol/L)+E2 (10 nmol/L) for 24 h.MTT kit was used to detect cell viability.Post-synaptic Density 95 protein expression was measured by western blot.ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell.Results Campared to Sham,LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF (P＜0.05),campared to LCT,LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF (P＜0.05),campared to E2,E2+TrkB FC could reduce the expression of PSD95 and E2+ICI could reduce the expression of BDNF (P＜0.05),campared to E2,LCT+ E2 could reduce the expression of PSD95 and BDNF (P＜ 0.05).Conclusion BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells.Although LCT alone has a similar effect on E2.LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.