Huatan Tongmai Yin regulates RFRP-3 to intervene in the "microbe-gut-HPO axis" to treat PCOS-IR rats.

OBJECTIVE

To explore the therapeutic effect of Huatan Tongmai Decoction on insulin-resistant polycystic ovary syndrome (PCOS-IR) and the potential mechanism.

METHODS

The PCOS-IR rat model was constructed and HE staining was used to observe the morphological changes of vaginal shedding cells and ovary. Serum sex hormone levels, fasting insulin (FINS), fasting blood glucose (FBG) and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Intestinal flora was analyzed by 16SrDNA sequencing. The mRNA expression of RFRP-3 and GPR147 in hypothalamus tissues was detected by RT-qPCR. The expression of ZO-1 and Occludin in colon tissue and the expression of GPR54, MyD88, TLR4, GnRHR and KP in the hypothalamus were detected by Western blot.

RESULTS

Compared with the model group, the body weight of the Huatan Tongmai Yin group decreased, the estrus cycle returned to normal, the levels of serum T, LH, FINS, HOMA-IR and inflammatory factors decreased, the levels of FSH increased, the types of intestinal flora OTU were more abundant, ACE and Chao index increased, and the mRNA level of hypothalamus RFRP-3 was up-regulated. In addition, serum T, LH, FPG, FINS and HOMA-IR levels were decreased, FSH levels were increased, inflammatory factors were down-regulated, and hypothalamic GPR54, MyD88, TLR4 and GnRHR proteins were reduced in rats after overexpression of RFRP-3.

CONCLUSION

Tantongmai Decoction can correct the imbalance of intestinal flora, improve intestinal mucosal barrier function, relieve chronic inflammation and insulin resistance, thus up-regulating RFRP-3 in the hypothalamus, inhibiting the release of GnRH and KP, reducing the secretion of LH and T, and effectively alleviating PCOS-IR by regulating "microbe-gut-HPO axis".