Objective To investigate the protective effect of Lycium barbarum polysaccharide (LBP) on reproductive system damage induced by exposure to high-altitude hypoxic environment in female rats, and to explore the mechanisms involved.

Methods After undergoing physiological synchronization, 30 female Wistar rats were randomly and evenly assigned to 3 groups, including a plain control (C) group, a high-altitude hypoxia (H) group, and a high-altitude hypoxia + LBP (H-LBP) group. The C group was placed in a region at an altitude of 1500 m above sea level (with an oxygen volume fraction of 18.55%), while the H group and the H-LBP group were placed in a region at an altitude of 4010 m above sea level (with an oxygen volume fraction of 12.70%). Rats in the H-LBP group were fed with LBP at 75 mg/kg via gastric gavage, while the C and H groups received normal saline once a day for 14 days in a row. Changes in estrous cycles were documented throughout the experiment. At the end of the experiment, the serum levels of reproductive hormones and the levels of oxidative stress in the ovarian and uterine tissues were measured. Morphological changes in the ovarian and uterine tissues were assessed using hematoxylin-eosin (HE) staining. A component-target-pathway network diagram was constructed using network pharmacology methods to analyze the key targets and pathways.

Results Compared with the C group, rats in the H group had disrupted estrous cycles and significantly lower serum levels of reproductive hormones (all P<0.05). In addition, rats in the H group had increased oxidative stress damage and experienced pathological damage in the ovarian and uterine tissues. However, compared with those of the H group, the estrous cycle in the H-LBP group became normalized after the administration of LBP and the serum levels of estradiol (E2), progesterone (P), luteinizing hormone (LH), and anti- Müllerian hormone (AMH) were significantly increased in H-LBP group (all P<0.05). In the ovarian tissue, the malondialdehyde (MDA) content was significantly reduced, superoxide dismutase (SOD) activity was increased, and the content of reduced glutathione (GSH) was increased. In addition, in the uterine tissue, the MDA content was reduced and SOD activity was increased (all P<0.05), with LBP significantly improving the pathological damage to the reproductive organs of female rats caused by high-altitude hypoxic environment. Through network pharmacology analysis, we identified 76 potential targets for the protective effect of LBP against high-altitude hypoxia-induced reproductive injury, and the targets were mainly involved in the signaling pathways such as calcium channels, PI3K-Akt, MAPK, and HIF-1.

Conclusion LBP can ameliorate high-altitude hypoxia-induced reproductive damage in female rats. The mechanisms involved may be associated with the regulation of PI3K-Akt, MAPK, and HIF-1 pathways.