[The mechanism of alleviation of paraquat induced vascular endothelial permeability by erythromycin through adenosine 3'5'-cyclic monophosphate pathway].
OBJECTIVE
To discuss the effects of erythromycin in protecting against paraquat induced vascular endothelial cell permeability and the possible molecular mechanism of the affect.


METHODS
The transwell was used to culture human umbilical vein endothelial cells (HUVEC) in vitro. The cultured endothelial cells were divided into three groups: control group (N group), paraquat group (P group), paraquat+ erythromycin group (P+E group). The variables were measured under different conditions at 6, 12, 36 and 48 hours by immunofluorescence and immunoradiometric assay to determine the changes in vascular endothelial permeability to macromolecules and the change in adenosine 3'5'-cyclic monophosphate (cAMP) concentration ([cAMP]).


RESULTS
(1) Endothelial permeability was steady in N group. The permeability in P group was increased, and it was higher than N group at 36 hours and 48 hours with statistical significance (P<0.01 and P<0.05). The permeability of P+E group was lower than P group and was higher than N group at 36 hours (both P<0.01), and there was no difference between N group and P+E group at 48 hours. (2) The [cAMP] was stable in N group at different time points; [cAMP] was decreased in P group with statistical significance at 24 hours as compared with N group (P<0.05). [cAMP] was elevated in P+E group, and it was higher than that of P group after 24 hours (P<0.05 or P<0.01); moreover, [cAMP] of P+E group was higher than that of N group at 48 hours (P<0.01). Endothelial permeability and [cAMP] was significantly negatively correlated in both P group and P+E group ( r(1)=-0.913, r(2)=-0.648, both P<0.05).


CONCLUSIONS
Erythromycin could improve the function of damaged vascular endothelial cell barrier after paraquat poisoning, and it was the result of lowering of cellular permeability due to elevation of endothelial cAMP.
Du
Yu
Y
Emergency Department, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
He
Qing
Q
D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D010269:Paraquat / Q000506:poisoning*; D014471:Umbilical Veins / Q000166:cytology
D004917:Erythromycin; D000242:Cyclic AMP; D010269:Paraquat