Effect of lead exposure on function of blood-cerebrospinal fluid barrier and ZO-1 and occludin protein expression in vitro / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To establish an in vitro blood-cerebrospinal fluid barrier (BCB) model to investigate the underlying mechanism of lead-induced BCB injuries.METHODS The in vitro BCB model was established by Z310 cells.Different concentrations of Pb(AC)2 (2.5,5.0 and 10.0 mmol·L-1) were used for 24,48 and 72 h.Transendothelial electrical resistance (TEER) and flux of FITC-dextran were performed to determine the permeability of the in vitro BCB model.Western blotting and immunofluorescence methods were used to observe the expression of tight junction protein ZO-1 and occludin.RESULTS Compared with control group,Pb(AC)2 2.5,5.0 and 10.0 mmol· L-1 exposure for 48 h to Z310 cells had no significant effect on survival rate and density.TEER in different groups was gradually increasing.At the 12th day after Pb(AC)2 exposure,the values of TEER and flux of FITC-dextran in Pb(AC)2 5 and 10 mmol· L-1 groups were significantly decreased (P＜0.05).Western blotting and immunofluorescence images showed that the expression of ZO-1 and occludin were significantly decreased (P＜0.05) after Pb(AC)2 exposure for 48 h.CONCLUSION Lead exposure can cause the breakdown of BCB barriers,and this effect may be mediated by reducing the expression of ZO-1 and occludin proteins.