Abstract: Objective:To investigate the improvement effect of estradiol valerate combined with aspirin on the intrauterine adhesion (IUA) in the rats, and to elucidate the therapeutic mechanism of estradiol valerate combined with aspirin. Methods:Fifty healthy female SD rats were randomly divided into control group, model group, estradiol valerate group, aspirin group,and estradiol valerate combined with aspirin group (combination group)(n=10);the rats in the other groups except control group were used to establish the IUA models with double injury method of uterine curettage and infection. The serum and uterine tissue were taken from the rats in each group 24 h after continuous administration, the estradiol levels in serum of the rats were observed by ELISA, and the pathological changes and the number of glands in the uterine cavity of the rats in various groups were observed by HE staining, and the ratio of endometrial fibrosis are a was observed by Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) in the endometrium of the rats were detected by immunohistochemistry. Results:The results of ELISA indicated that the estrodiol level in serum of the rats in model group was significantly lower than that in control group(P<0.05);compared with model group,the estrodiol levels in serum of the rats in estradiol valerate group, aspirin group, and combination group were significantly increased (P<0.05). The results of HE and Masson staining showed that compared with control group, uterine cavity adhesion and enlargement, fluid accumulation in the cavity, disorganized arrangement of the cells of uterine cavity wall, significant infiltration of inflammatory cells, endometrial stroma fibrosis,and disordered collagenous fibers were found in model group; the number of endometrial glands in the rats was significantly decreased(P<0.05),and the fibrosis area ratio was significantly increased (P<0.05). Compared with model gorup,the adhesion and effuson in uterine cavity,inflammatory cell infiltration and endometrial stroma fibrosis were alleviated,the cells of uterine cavity wall were arranged neatly,and there was little collagenous fibers in estradiol valerate group,aspirin group,and combination group;the number of endometrial glands was increased(P<0.05),and the fibrosis area ratios were significantlhy decreased(P<0.01).Compared with aspirin group,the number of endometrial glands in combination group was significantly increased(P<0.05),and the fibrosis area ratio was significantly decreased(P<0.05).Compared with model group, the expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in estradiol valerate group, aspirin group, and combination group were significantly decreased (P<0.05 or P<0.01), and the expression levels of MMP-9 protein in the endometrium tissue were significantly increased (P<0.05).The expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in combination group were significantly lower than those in aspirin group (P<0.05), and the expression level of MMP-9 in the endometrium tissue was significantly higher than that in aspirin group (P<0.05). Conclusion:Estradiol valerate combined with aspirin can decrease the expression levels of TGF-β1 and PAI-1 in the endometrium tissue and increase the expression level of NMP-9, which can improve the IUA of the rats.

Key words: intrauterine adhesions, estradiol valerate, aspirin, transforming growth factor-β1, plasminogen activator inhibitor type-1, matrix metalloproteinase-9