Purpose: To investigate the estrogenic protective effect and mechanism of Tanshinone IIA on oxidative-injured vascular endothelial cells.
Methods: We established low-estrogen atherosclerotic animal model by feeding ovariectomized apoE-/- mice a high-fat diet, and oxidative-injured cells model were induced by ox-LDL in HUVECs. Tanshinone IIA ( mice: 30mg/kg, 60mg/kg, cells: 0.1μM, 1μM, 10μM) was given to the mice and cells, and estrogen(mice: 0.00013mg/g/d, cells: 0.01μM) and estrogen receptor antagonist(ICI182780, mice: 0.065mg/g, cells: 0.1μM) were also designed to be given. The levels of NF-κB, sICAM-1, AP-1, E-selectin and 17β-estradiol (E2) in serum and the levels of NF-κB, sICAM-1, AP-1 and E-selectin in supernatant were measured by ELISA. The expression of p-ERK1/2 in cells and mice aorta and expression of ERα in cells were assessed by Western blotting.
Results:Tanshinone IIA could not significantly increase the serum E2 level of ovariectomized apoE-/- mice. But it significantly inhibited the levels of NF-κB, AP-1, sICAM-1 and E-selectin in serum of ovariectomized ApoE-/- mice and supernatant of ox-LDL injured HUVECs, and Tanshinone IIA significatly inhibited the expression of p-ERK1/2 in mice aorta and cells and inhibited the expression of ERα in cells, which was similar to the estradiol, and could be inhibited by ICI182780.
Conclusios: Tanshinone IIA has an anti-inflammatory effect on oxidative-injured cells, and the mechanism is that Tanshinone IIA could significantly attenuate the p-ERK1/2 to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway by bonding with estrogen receptor, which is similar to the estrogen.