黄连素对PCOS大鼠肠道菌群以及LPS/NF-κB信号通路的影响

Effects of berberine on intestinal flora and LPS/NFκB signaling pathway in PCOS rats

【目的】探讨黄连素对PCOS模型大鼠血清性激素水平、肠道菌群以及LPS/NF-κB信号通路的影响。【方法】将SD大鼠随机分成对照组、模型组[来曲唑1 mg/(kg·d)]、达英-35组[0.18 mg/(kg·d)]、二甲双胍组[0.135 g/(kg·d)]、黄连素组[0.216 g/(kg·d)]以及黄连素+二甲双胍+达英-35(3种药物合用)组,每组10只,灌胃28 d,检测大鼠体质量,用ELISA法检测血清性激素水平、胰岛素指数(HOMA-IR)、脂多糖(LPS)、白介素1(IL-1β)、肿瘤坏死因子α(TNF-α)和干扰素γ(INF-γ)变化,用16s rDNA扩增子焦磷酸测序肠道菌群变化。【结果】黄连素和二甲双胍明显减低PCOS模型大鼠体质量,血清促黄体生成素(LH)和睾酮(T)水平,HOMA-IR、LPS和炎性因子水平表达,增加肠道菌群数量和多样性,增加拟杆菌门(Bacteroidetes)、变形菌门(Proteobacteria)、放线菌门(Actinobacteria)、疣微菌门(Verrucomicrobia)、拟杆菌属(Bacteroides)、乳酸菌属(Lactobacillus)、双歧杆菌属(Bifidobacterium)和萨特氏菌属(Sutterella)相对丰度,降低厚壁菌门(Firmicutes)、普氏菌属(Prevotella)、瘤胃球菌属(Oscillospira)、颤螺菌属(Oscillospira)和厌氧菌属(Anaeroplasma)相对丰度。【结论】黄连素降低PCOS模型大鼠高雄激素和高胰岛素血症作用机制可能与抑制LPS/NF-κB信号通路,提高肠道有益菌相对丰度,降低致病菌相对丰度有关。

【Objective】To investigate the effects of berberine on serum sex hormone levels,intestinal flora and LPS/NF-κB signaling pathway in PCOS model rats.【Method】SD rats were randomly divided into control group,model group[Letrozole 1 mg/(kg·d)],dae-35 group[0.18 mg/(kg·d)],metformin group[0.135 g/(kg·d)]and berberine group[0.216)g/(kg·d)]and berberine+metformin+daca-35(3 drugs combined),10 rats in each group.And all rats were treated for 28 d with gavage.Body weight was measured.Serum sex hormone levels,insulin index(HOMA-IR),adiponectin(LPS),interleukin-1β(IL-1β),tumor necrosis factorα(TNF-α)and interferonγ(INF-γ)were detected by ELISA,and intestinal microflora was sequenced by 16s rDNA ampli.【Result】Berberine and metformin significantly reduced body weight,serum luteinizing hormone(LH)and testosterone(T)levels,and the levels of HOMA-IR,LPS and inflammatory factors in PCOS model rats,and increased the number,diversity and evenness of intestinal bacteria.In particular,Bacteroidetes,Proteobacteria,Actinobacteria,Verrucomicrobia,Bacteroides,Lactobacillu,Bifidobacterium and Sutterella are increased,the relative abundances of Firmicutes,Prevotella,Oscillospira,Oscillospira,and Anaeroplasma are reduced.【Conclusion】The mechanism of berberine reducing hyperandrogen and hyperinsulinemia in PCOS model rats may be related to the inhibition of LPS/NF-κB signaling pathway and the increase of relative abundance of intestinal beneficial bacteria and the decrease of relative abundance of pathogenic bacteria.