Effects And Mechanism Of HIF-1? On The Permeability Of Rat Endothelial Cells

Objective To investigate the effects and mechanism of HIF-1? on the permeability of rat aortic endothelial cells.Methodes Interference and overexpression vector of HIF-1? was transfectant into rat aortic endothelial cells by Lipofectamine 2000 respectively.Rat aortic endothelial cells were cultured at a concentration of 200?g/m L G418.The expression of HIF-1?,ET-1,ETA,ETB and ZO-1 was detected by Real-time PCR and Western blot.The signal transduction inhibitor BQ123 and BQ788 was applied to discover the activity changes of HIF-1?/ET-1 sigmal.Meanwhlie,the membrane permeability coefficient of the monolayer endothelial cells was examined.Results Compared with the control group,the levels of HIF-1? and ET-1 in the scalded rats were significantly increased(P<0.01,P<0.01).Compared with the control group,the m RNA and protein expression levels of HIF-1?,ET-1,ETA and ETB were significantly decreased in the transfected HIF-1? interfered group(P<0.01),while the expression of ZO-1 was obviously increased(P<0.01).The results of transfection of the HIF-1? overexpression vector group were reversed.At the same time,the cell membrane permeability coefficient was significantly increased(P<0.01),and the cell membrane permeability coefficient was decreased after treatment with BQ123 and BQ788.It could inhibit the expression of ETA and ETB induced by HIF-1a and enhance the expression of ZO-1,and the permeability coefficient of cell membrane was significantly decreased(P<0.01).Conclusion HIF-1? can increase the permeability of rat aortic endothelial cells by up-regulating the expression of ET-1.And,the HIF-1?/ET-1 signal axis plays an important role in regulating vascular permeability in burned rats.