丝裂原活化蛋白激酶抑制剂SB203580可通过下调小鼠模型的促炎细胞因子和蛋白水解因子抑制子宫内膜异位症发病

p38 mitogen-activated protein kinase (p38 MAPK), a regulator of inflammation, may play a role in the pathogenesis of endometriosis (EM). We studied the effect of SB203580, a p38 MAPK inhibitor, on the development of EM in a mouse model. Methods EM was induced in BALB/c mice by peritoneal injection of endometrium-rich fragments. Mice (n = 15) were injected i.p. for 24 days with SB203580 and 15 mice served as positive controls (EM group). Sham-operated mice received carrier only. Peritoneal fluid (PF) cells were collected for protein/mRNA analysis. Interleukin (IL)-1, tumor necrosis factor (TNF)-, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins were measured using enzyme-linked immunosorbent assay and mRNAs by RT-PCR. Phosphorylation of p38 MAPK was evaluated by western blotting. Results SB203580 decreased the weight and size (P < 0.05 versus EM) of endometriotic lesions in BALB/c mice. IL-1, TNF-, MMP-2 and MMP-9 mRNA levels were decreased in peritoneal cells of the SB203580 versus EM group (P < 0.01, P < 0.05, P < 0.05 and P < 0.05, respectively). Concentrations of IL-1, TNF-, MMP-2 and MMP-9 proteins in PF were reduced in the SB203580 versus EM group (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). Compared with the sham-operated group, phosphorylation of p38 MAPK in the EM group was increased, and this was down-regulated by SB203580 (P < 0.01). Conclusions SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.