Abstract: Objective To study the molecular mechanism of placental growth factor (PLGF) inducing brain vascular endothelial cell tight junctions’ opening. Methods Using human brain microvascular endothelial cells (HBMECs) to construct blood-brain barrier (BBB) modal in vitro, with which to study human recombinant PLGF protein inducing the change of electrical resistance (TEER) and permeability of the BBB. Moreover, the distribution and change of tight junction protein ZO-1 and occludin were observed by immumofluorescence and Western blotting methods to confirm the effects of PLGF on tight junction of BBB. Finally, detected the cell signals induced by PLGF on tight junction of BBB using protein inhibitors and Western blotting method.Results PLGF induced a decrease of TEER and an increased of HRP flux of BBB modal in vitro. Besides, PLGF increased soluble occludin and changed ZO-1 distribution, the inhibitor of ROCK (Y27632) blocked the HRP flux induced by PLGF, and RhoA-GTP was decteced in HBMEC after PLGF tratement. Conclusion PLGF induces tight junction’s opening of BBB in virto by activation Rho/ROCK signaling.

Key words: placental growth factor, blood-brain barrier, tight junction, Rho/ROCK