Abstract: OBJECTIVE: To investigate the therapeutic effect of Er-Xian decoction( 二仙汤, EXD) on the autoimmune premature ovarian failure(POF) in mice, and its regulatory mechanisms.METHODS: Female BALB mice were treated with a single intraperitoneal injection of zona pellucida 3(ZP3). One week later, mice received low(5 g/kg),moderate(10 g/kg) and high(20 g/kg) doses of EXD by gastrogavage once daily for 90 d. Premarin(0.03 mg/kg) served as the positive control group. Serum levels of estradiol(E2), follicle stimulating hormone(FSH) and luteinizing hormone(LH) were measured by enzyme-linked immunosorbent assay, lymphocyte subtypes were analyzed, and follicular structure differences were observed by hematoxylin andeosin staining. The main mechanisms of POF was investigated by immunohistochemical analysis.RESULTS: Serum E2 levels in POF model mice were decreased, whereas FSH and LH levels were dramatically increased. Serum levels of LH and FSH were reduced in POF model mice treated with EXD(moderate and high doses) and premarin, while serum level of E2 were increased after POF model mice had been treated with EXD and premarin. The CD3+ T, CD4+ T, CD4+ T/CD8+ T ratio of mice in the positive control group and high and medium dose groups of EXD increased(P < 0.05), and the number of CD8 + T cells decreased significantly(P < 0.05)when compared with the model group. Bone morphogenetic protein 15(BMP15) and Akt were repressed in autoimmune POF model mice, whereas high expression was observed in control mice and those treated with EXD(moderate and high doses)and premarin.CONCLUSION: EXD is effective in treating ZP3-induced POF in mice and increased expression of BMP-15, and Akt is represented in the mechanism accounting for this therapeutic effect.

Key words: autoimmune diseases, primary ovarian insufficiency, zona pellucida, bone morphogenetic protein 15, Er-xian decoction