Objective(s): We looked into the ameliorative effects of Grifola frondosa Polysaccharides(GFPS)on ovarian fibrosis in rats with letrozole-induced polycystic ovary syndrome(PCOS),and we also looked into the precise molecular mechanisms behind such ameliorative effects.Method(s): Letrozole(1 mg/kg·day)was administered to establish the PCOS animal model,while GFPS(600 mg/kg·day)and Met(265 mg/kg·day)were administered to create the intervention over the course of 21 days.Every three days during the modeling phase,the rats’ body weight was recorded.On the tenth day of the modeling period,the rats were stained with Pap to observe changes in the estrous cycle,and H&E to observe histological changes in the rat ovaries.And Masson staining was used to measure the ovarian fibrosis region.The rat sex hormones(T,LH,FSH and E2),lipids(TC,TG,LDL-C and HDL-C),oxidative stress(MDA,SOD and GSH-Px),fasting blood glucose(FBG),and fasting insulin(FINS)levels were all measured by the ELISA kit.RT-q PCR was used to identify the m RNA expression of anti-oxidant enzymes and inflammatory factors in rat ovarian tissues.Western Blotting and immunohistochemistry were used to identify the expression of the TGF-β1/Smads main pathway and fibrogenic factors.Result(s): GFPS dramatically lowered body weight,relative ovarian mass,and volume,considerably decreased the number of cystic follicles and atretic follicles in PCOS rats,and raised the number of regularly developed follicles,corpus luteum,and granulosa cells.It also corrected the irregular estrous cycle of PCOS rats.Furthermore,GFPS alleviated the disruption of sex hormone levels,decreased the HOMA-IR(insulin resistance index),and fixed aberrant lipid metabolism and serum oxidative stress levels in PCOS rats.Additionally,in the ovarian tissues of PCOS rats,GFPS increased the expression of the antioxidant enzymes Cat,Sod2,Gpx3,Mgst1,Gsta4,Sod1,Gsr,and Prdx3 and decreased the m RNA expression of the inflammatory markers Nlrp3,Asc,Caspase1,Il1β,Il18,Tnfα,and Il6.It also reduced TGF-β1,TGF-βR1,p-Smad2/Smad2,p-Smad3/Smad3,and Smad4 while increasing the production of Smad7 and PPAR-γ proteins,which helped to treat ovarian fibrosis.Conclusion(s): In summary,GFPS improved serum levels of sex hormones and lipid metabolism,reduced HOMA-IR,regulated oxidative stress and chronic inflammation in PCOS rats,and ultimately improved ovarian fibrosis in PCOS rats by regulating the molecular mechanism of TGF-β1/Smads signaling pathway. |