基于TLR-4/MyD88/NF-κB通路探讨粪菌移植对多囊卵巢综合征大鼠的治疗作用OA

Objective To explore the potential mechanism of fecal microbiota transplantation(FMT)in the treatment of polycystic ovary syndrome(PCOS)model rats through TLR-4/MyD88/NF-κB signaling pathway.Methods Thirty female SD rats aged 6-8 weeks were randomly divided into control group,model group and fecal microbiota transplantation group.The PCOS model was established by intragastric administration of trazol for 21 days in the model group.After successful modeling,FMT intervention was performed.The body weight was weighed every 7 days,and the estrous cycle was observed by vaginal smear.The rats were fasted for 12 hours before being sacrificed,and the levels of fasting plasma glucose(FPG),fasting insulin(FINS)and Homeostatic Model Assessment for Insulin Resistance(HOMA-IR)were detected.The levels of testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(LH),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and lipopolysaccharide(LPS)in serum were detected by ELISA.HE staining was used to observe the pathological changes of ovarian tissue,and Western Blot was used to detect the expression levels of TLR-4,MyD88 and NF-κB protein in ovarian tissue of rats in each group.Results Compared with the control group,the body weight,ovarian weight and ovarian weight/body weight of the rats in the model group were significantly increased,the estrous cycle was disordered,the ovarian tissue showed multiple follicular changes,the levels of serum T,LH,LH/FSH and HOMA-IR were increased,the level of FSH was decreased,the level of LPS was significantly increased,the levels of pro-inflammatory factors IL-1 β,IL-6 and TNF-α were increased,the level of anti-inflammatory factor IL-10 was decreased,and the expression levels of TLR-4,MyD88 and NF-κB protein were increased(P<0.05).Compared with the model group,the body weight,ovarian weight and ovarian weight/body weight of the rats in the fecal microbiota transplantation group were significantly decreased,the estrous cycle of the rats was significantly restored,the dominant follicles and corpus luteum were observed in the ovarian tissue,the levels of serum T,LH,LH/FSH,HOMA-IR and LPS were decreased,the levels of pro-inflammatory factors IL-1β,IL-6 and TNF-α were decreased,the level of anti-inflammatory factor IL-10 was increased,and the expression levels of TLR-4,MyD88 and NF-κB proteins were decreased(P<0.05).Conclusion Fecal microbiota transplantation can reduce the body weight of PCOS rats,reduce androgen levels,improve HOMA-IR,inhibit TLR-4/MyD88/NF-κB signaling pathway,reduce the expression of LPS and inflammatory factors,improve chronic inflammation and restore ovarian function.