中药药理与临床2026，Vol.42Issue(4)：51-58,8.
银杏二萜内酯通过调控TLR4/MyD88/NF-κB信号通路改善多囊卵巢综合征大鼠卵巢功能
Effect of Ginkgo Diterpene Lactones on Improving Ovarian Function in Rats with Polycystic Ovary Syndrome by Regulating TLR4/MyD88/NF-κB Signaling Pathway
摘要
Abstract
Objective:To investigate the effect and potential mechanism of ginkgo diterpene lactones on ovarian function in rats with polycystic ovary syndrome(PCOS).Methods:According to the random number table method,48 specific-pathogen free(SPF)female Sprague Dawley(SD)rats were randomly divided into a normal control group,a model control group,a metformin group of 100 mg/kg(intragastric administration),ginkgo diterpene lactone groups of 1.2,2.4,and 4.8 mg/kg(intraperitoneal injection),with eight rats in each group.Modeling rats were intragastrically administered with 1 mg/kg letrozole combined with a high-fat diet for 28 days to establish a PCOS rat model.After mod-eling,rats in each group were given corresponding drugs or saline water,once a day for 14 days.The fasting blood glu-cose(FBG)and fasting insulin(FINS)were measured,and the homeostatic model assessment for insulin resistance(HOMA-IR)was calculated.The body mass and ovarian mass were weighed,and the ovarian index was calculated.The level of sex hormones[estradiol(E2),testosterone(T),gonadotropin-releasing hormone(GnRH),follicle stimulating hormone(FSH),and luteinizing hormone(LH)]in serum and the level of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6]in ovarian tissue were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes in the ovary were examined by hematoxylin eosin(HE)staining,and the number of cystic follicles and corpus luteum was counted.The mRNA expression of toll-like receptor 4(Tlr4),myeloid differentia-tion factor 88(Myd88),and nuclear factor kappa B p65(Nfκb p65)in ovarian tissue was detected by reverse transcrip-tion polymerase chain reaction(RT-PCR).The protein expression of TLR4,MYD88,cytoplasmic NF-κB p65,and nucle-ar NF-κB p65 was detected by Western blot.Results:Compared with those in the normal control group,the FBG,FINS,HOMA-IR,body mass,and ovarian index of the rats were significantly increased in the model control group(P<0.01).The levels of T,GnRH,and LH in serum,and LH/FSH were significantly increased,while the level of E2 and FSH was significantly decreased(P<0.01).The level of TNF-α,IL-1β,and IL-6 in ovarian tissue was significantly increased(P<0.01).In ovarian tissue,polycystic dilation,increased large follicles,decreased mature follicles,disordered arrange-ment and decreased number of follicular granulosa layer,and decreased number of corpus luteum were observed.The number of cystic follicles was significantly increased,while the number of corpus luteum was significantly decreased(P<0.01).The mRNA expression of Tlr4,Myd88,and Nfκb p65 and the protein expression of TLR4,MYD88,cytoplasmic NF-κB p65,and nuclear NF-κB p65 in ovarian tissue were significantly upregulated(P<0.01).Compared with those in the model control group,the FBG,FINS,HOMA-IR,body mass,and ovarian index of the rats in the metformin group of 100 mg/kg and the ginkgo diterpene lactones groups of 2.4 and 4.8 mg/kg were significantly decreased(P<0.05 or P<0.01).The levels of T,GnRH,and LH in serum,and LH/FSH were significantly decreased,and the level of E2 and FSH was significantly increased(P<0.05 or P<0.01).The level of TNF-α,IL-1β,and IL-6 in ovarian tissue was sig-nificantly decreased(P<0.05 or P<0.01).The pathological changes in ovarian tissue were significantly improved.The number of cystic follicles was significantly decreased,while the number of corpus luteum was significantly increased(P<0.01).The mRNA expression of Tlr4,Myd88,and Nfκb p65 and the protein expression of TLR4,MYD88,cytoplasmic NF-κB p65,and nuclear NF-κB p65 in ovarian tissue were significantly downregulated(P<0.05 or P<0.01).The effects of the ginkgo diterpene lactone groups of 1.2,2.4,and 4.8 mg/kg on various detection indices(excluding the body mass,GnRH,and IL-6)showed a dose-dependent way(P<0.05 or P<0.01).Conclusion:Ginkgo diterpene lac-tones can effectively improve the ovarian function of PCOS rats by regulating the level of endocrine and inhibiting inflam-mation.The above effects of ginkgo diterpene lactones are dose-dependent,and their mechanism may be related to the in-hibition of the TLR4/Myd88/NF-κB signaling pathway.关键词
多囊卵巢综合征/银杏二萜内酯/卵巢功能/炎症/Toll样受体4/髓样分化因子88/核因子-κB信号通路Key words
Polycystic ovary syndrome/Ginkgo diterpene lactone/Ovarian function/Inflammation/Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway引用本文复制引用
张红霞,王莉平,曹亚茹,冯梅梅..银杏二萜内酯通过调控TLR4/MyD88/NF-κB信号通路改善多囊卵巢综合征大鼠卵巢功能[J].中药药理与临床,2026,42(4):51-58,8.基金项目
邯郸市科学技术研究与发展计划项目(编号:23422083221) （编号:23422083221）
石家庄市科学技术研究与发展指导计划课题(编号:141463073). （编号:141463073）
