Protects Against the Oxidative Injury Induced by Cold Stress in Ovaries by the SIRT1/FOXO1 Pathway in Moxibustion

Objective This study aimed to investigate the role of the SIRT1/FOXO1 pathway in mediating the protective effects of moxibustion on ovarian function in a chronic cold stress rat model. Methods A chronic cold stress model was established through ice-water immersion and cold exposure. Rats received mild moxibustion at the Guanyuan (CV4) point. Estrus cycle and ovarian morphology were assessed. Serum levels of E2, follicle-stimulating hormone (FSH), luteinizing hormone (LH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and oxidative markers [SOD, malondialdehyde (MDA)] were measured. Ovarian transcriptome sequencing was performed. The SIRT1 inhibitor EX527 was administered to validate pathway involvement, with protein expression of SIRT1/FOXO1 and oxidative factors [manganese superoxide dismutase (MnSOD), CAT] analyzed. Results Chronic cold stress prolonged the estrus cycle; disrupted ovarian structure; lowered serum E2, FSH, LH, and cAMP; increased cGMP; and induced oxidative stress (elevated MDA, reduced SOD). Transcriptome analysis linked chronic cold stress to the SIRT1/FOXO1 pathway. Chronic cold stress decreased ovarian SIRT1, FOXO1, MnSOD, and CAT protein expression but increased Ac-FOXO1. Moxibustion reversed all these alterations. Treatment with the SIRT1 inhibitor reversed the effects of moxibustion intervention on the expression of SIRT1, FOXO1, MnSOD, CAT, and Ac-FOXO1, with statistically significant differences ( P < 0.05). Conclusion Moxibustion can alleviate the chronic cold stress-induced ovarian injury and oxidative stress through the SIRT1/FOXO1 pathway and its antioxidative effects.