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The effects of artesunate on ovarian tissue morphology in rats with polycystic ovary syndrome
WEI Yi, ZHANG Shufen, HUANG Mengying, MA Yan△
2022, 50 (6):
588-594.
doi: 10.11958/20212673
Abstract: Objective To explore the effect of artesunate (ART) on the ovarian tissue morphology of a rat model of polycystic ovary syndrome (PCOS) based on the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB) signaling pathway. Methods The PCOS rat model was established by subcutaneous injection of dehydroepiandrosterone diluted with injection oil (once a day) for 28 days on SD female rats. A total of 120 rats with successful modeling were randomly divided into the PCOS group, the Diane-35 group, the ART low dose (25 mg/kg, ART-L) group, the ART high dose (50 mg/kg, ART-H) group and the ART-H+p38 MAPK specific activator (anisomycin) group, with 24 rats in each group. Another 24 rats were subcutaneously injected with the same amount of normal saline as the normal group. The rats in the Diane-35 group, the ART-L group, the ART-H group and the ART-H+anisomycin group were given corresponding drugs for 28 days, and the rats in the normal group and the PCOS group were given the same amount of normal saline, once a day. Giemsa staining was used to observe morphology of vaginal cells in ratestrous cycle. The fasting blood glucose (FPG) levels in rats were measured by automatic biochemical analyzer. Enzyme linked immunosorbent assay was used to detect the serum levels of fasting insulin (FINS), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), interleukin (IL)-18, tumor necrosis factor-α (TNF-α), and IL-1β. The insulin resistance index (HOMA-IR) was calculated. Ovarian histopathology and ultrastructure were observed by hematoxylin-eosin staining and transmission electron microscope, respectively. Western blot assay was used to detect the expression of p38 MAPK/NF-κB pathway protein in ovarian tissue. Results Compared with the normal group, rats in the PCOS group had abnormal estrous cycle, decreased serum levels of LH, T, FPG, FINS, HOMA-IR, IL-1β, TNF-α and IL-18, decreased ovarian weight and number of follicles, heavier degrees of ovarian pathology and damage, increased expression levels of phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK, phosphorylated NF-κB p65 (p-NF-κB p65)/NF-κB p65 protein, and reduced levels of FSH and E2 (P＜0.05). Compared with the PCOS group, the serum levels of LH, T, FPG, FINS, HOMA-IR, IL-1β, TNF-α and IL-18 were decreased, ovarian weight and number of follicles were decreased, the degrees of ovarian pathology and damage were aggravated, the expression levels of p-p38 MAPK/p38 MAPK, p-NF-κB p65/NF-κB p65 protein were reduced, and FSH and E2 levels were increased in the Diane-35 group, the ART-L group and the ART-H group (P＜0.05). Compared with the Diane-35 group, there were no significant differences in the above indicators in the ART-H group (P＞0.05). Compared with the ART-H group, the serum levels of LH, T, FPG, FINS, HOMA-IR, IL-1β, TNF-α and IL-18 were increased, ovarian weight and number of follicles were increased, the degrees of ovarian pathology and damage were aggravated, expression levels of p-p38 MAPK/p38 MAPK, p-NF-κB p65/NF-κB p65 protein were increased, and the levels of FSH and E2 were reduced in the ART-H+anisomycin group (P＜0.05). Conclusion ART may restore the level of sex hormones and improve the morphology and function of ovarian tissue in PCOS rats by inhibiting the p38 MAPK/NF-κB inflammatory pathway.
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