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Citation
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Tian H, Ouyang YS, Ding SS, Wang R, Kong N, Wang ZY, Shen L, Lu M, Zhang XT, Wu J, Hu HB, Zhou JS. J. Xian Jiatong Univ. Med. Sci. 2018; 39(6): 825-830. |
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Abstract
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OBJECTIVE: To evaluate the effects of metformin therapy on the expressions of factor associated suicide (Fas) and Fas ligand in rat ovaries with polycystic ovary syndrome (PCOS) induced by DHEA so as to explore the molecular mechanism of metformin treatment of PCOS.
METHODS: Totally 30 SD female rats aged 85 days were randomly divided into PCOS group (n=10), metformin (dimethylbiguanide, DB) therapy group (n=10), and control group (n=10). DHEA hypodermic injection was adopted to establish PCOS rat model in the first two groups, followed by administration of the placebo or metformin respectively, and similarly dissolvent injection and placebo in control group rats were introduced. After 14 days' treatment, ovaries taken from the rats in each group were weighed, and their structural changes were observed with HE staining. The serum levels of insulin, luteinizing hormone and testosterone were tested by ELISA, and the changes of Fas and Fas ligand expressions were detected by immunohistochemistry and Western blot.
RESULTS: ① We found significant increases in weight, volume, average ovarian surface area, maximum follicular diameter and follicular theca thickness of the rats in PCOS group compared with those in control group (all P<0.05). Remarkable declines in all the items above occurred in DB therapy group compared with PCOS group (all P<0.05). ② The serum INS, LH and T in PCOS and DB therapy groups were markedly increased compared with those in the control group, and a sharp decrease in serum T was detected in the rats of DB therapy group in comparison with PCOS group (all P<0.05). ③ Fas and FasL were mainly located in the cytoplasm of granulosa cells of antral follicles. The expressions of the two proteins were strong in granulosa cells of the thinner layers close to the follicular antrum in dilated follicles of PCOS group In addition, weak expressions of Fas and FasL were observed in the cytoplasm of oocytes and zona pellucida of primary follicles. ④ Significant increases in expressions of Fas and FasL in ovaries of PCOS group were found compared with the control group (P<0.05, P<0.05). However, the expression of Fas in the rats of DB therapy group showed distinct drop compared with the control and PCOS groups (P<0.05, P<0.05). Moreover, marked increase in FasL expression existed in DB therapy group compared with the control group (P<0.05).
CONCLUSION: Establishment of PCOS rat model by DHEA hypodermic injection is completely feasible. The Fas/FasL pathway is pivotal for abnormal apoptosis of the follicles in the ovaries. Moreover, DB therapy may partially reverse the polycystic changes. © 2018, Editorial Board of Journal of Xi'an Jiaotong University (Medical Sciences). All right reserved.
Language: zh |