Electroacupuncture Regulates Insulin Resistance, Histone Acetylation, and Oxidative Stress in a Rat Model of Polycystic Ovary Syndrome

Objective: Acupuncture is effective in the treatment of polycystic ovary syndrome with insulin resistance (PCOS-IR), but the underlying mechanism is still unclear. In this study, we further investigated the regulatory effects of electroacupuncture (EA) on IR, histone acetylation, and oxidative stress in PCOS-IR rats. Materials and Methods: PCOS-IR rats were induced with letrozole combined with a high-fat diet. EA at Yinsanzhen (CV4, SP6, and ST29) was performed daily for 3 weeks. Fasting blood glucose and area under the curve were assessed through a glucose tolerance test. Ovarian morphology was observed through hematoxylin and eosin staining. The levels of glucose and lipid metabolism and reproductive endocrine parameters in the rats were evaluated with a test kit. RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the gene expression. Results: EA significantly improved the regularity of the estrous cycle, ovarian morphology, glucose-lipid metabolism, and reproductive endocrine system in PCOS-IR rats. RNA‒seq revealed that EA had certain regulatory effects on the HDAC1, NRF1, Mfn1, OPA1, Drp1 (Dnm1I), and Fis1 genes. RT-qPCR further verified that EA significantly upregulated the mRNA expression of HDAC1, histone H4, OPA1, and Fis1 and tended to decrease the level of the AKT mRNA. Conclusions: EA can improve the pathological manifestations of the ovary, glucose-lipid metabolism, and reproductive endocrine system in PCOS-IR model rats. EA can increase the expression of HDAC1 and histone H4. In addition, EA can increase the expression of OPA1 and Fis1, decrease the expression of AKT, to reduce oxidative stress and improve IR.