中国中西医结合杂志2025，Vol.45Issue(4)：462-474,13.DOI:10.7661/j.cjim.20250120.102
清腑导痰汤改善多囊卵巢综合征伴胰岛素抵抗作用机制
Mechanism of Qingfu Daotan Formula for Improving polycystic ovary syndrome-insulin resistancet
摘要
Abstract
Objective To study the mechanism of Qingfu Daotan(QFDT)Formula in improving polycystic ovary syndrome-insulin resistance(PCOS-IR)based on intestinal flora.Methods Totally 65 female SD rats with normal estrous cycle were divided into 6 groups according to the weight stratified randomization method:control group,PCOS-IR group,metformin group,QFDT-low dose group(QFDT-L),QFDT-normal dose group(QFDT-N),and QFDT-high dose group(QFDT-H).Except for the control group,rats in the other five groups were administered with high-fat diet combined with letrozole by gastrogavage for 4 successive weeks to establish the dynamic model of PCOS-IR rats.Rats in the QFDT-L,QFDT-N,and QFDT-H groups were given 4.8,9.6,and 19.2 g/kg QFDT per day by gastrogavage respectively,and rats in the Metformin group was given 0.1 g/kg metformin per day by gastrogavage.The administration lasted for 4 successive weeks.The following indices were observed:the effects of QFDT Formula on serum hormone levels,insulin resistance(IR),inflammatory factors,and lipopolysaccharide(LPS)levels in PCOS-IR rats;the changes of intestinal histopathology;intestinal compact protein Occludin,ZO-1 gene and protein expressions;and the changes of intestinal bacterial flora compositions were subjected to the analysis of diversity,phyla level analysis,specific bacterial flora analysis,and specific bacterial flora-phenotypic correlation analysis.Results Compared with the control group,rats in the PCOS-IR group had significantly higher body weight and ovary weight(P＜0.01),and disturbed motility cycle;serum levels of luteinizing hormone(LH)/follicle stimulating hormone(FSH),testosterone(T),fasting plasma glucose(FPG),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),LPS,C-reactive protein(CRP),IL-6,IL-18,and tumor necrosis factor α(TNF-α)were significantly higher(P＜0.01);the number of cystic follicles significantly increased and the number of corpus luteum was lower in the ovarian tissue sections(P＜0.01);disrupted intestinal structure was seen in the intestinal tissue,and the expression of ZO-1,occludin protein and mRNA expressions in the intestinal tissue decreased(P＜0.05).Compared with the PCOS-IR group,the rat body weight and ovary weight of rats in the QFDT-N,QFDT-H,and metformin groups were significantly lower(P＜0.01,P＜0.05),and the proportion of the return of the motility cycle to normal increased;the serum levels of LH/FSH,T,FPG,FINS,HOMA-IR,LPS,CRP,IL-6,IL-18,and TNF-α significantly decreased(P＜0.05);the number of cystic follicles decreased and the number of corpus luteum increased in the metformin group and QFDT-H groups in the ovarian tissue sections(P＜0.01);and the disruption of the intestinal structure in the intestinal tissues was ameliorated,and increased expressions of ZO-1,occludin protein and mRNA occurred in the intestinal tissues(P＜0.05).In the analysis of intestinal flora,the alpha diversity-related indices(Observed_otus,Chao 1,Shannon,and Simpson indices)of intestinal flora in the PCOS-IR group all significantly decreased,as compared with the control group(P＜0.01);the abundance of Firmicutes phylum significantly decreased(P＜0.01),the abundance of Bacteroidota phylum significantly increased(P＜0.01),and the abundance of Firmicutes spp.decreased,and the abundance of Muribaculaceae spp.and Prevotella spp.increased(P＜0.05),and the QFDT group and PCOS-IR reversed the above changes in the flora.When comparing with the flora of the PCOS-IR group with that of the QFDT group,it was found that Prevotella spp,Muribaculaceae spp,Ruminococcus spp,Firmicutes_unclassified spp,Eubacterium_ruminantium spp,Roseburia spp,Quinella spp,Phascolarctobacterium spp,and Desulfovibrio spp were the specific differential genera between the two groups.These genera were associated with PCOS-IR host phenotypes(body weight,HOMA-IR,IL-6,IL-18,CRP,TNF-α)and LPS levels(P＜0.05).Conclusion QFDT Formula significantly improved the reproductive endocrine level and chronic inflammatory state of PCOS-IR rats.Its mechanism of action might be correlated to the regulation of intestinal flora structure,improving the intestinal mucosal barrier,and thus alleviating the chronic low-grade inflammatory state.关键词
多囊卵巢综合征/胰岛素抵抗/清腑导痰汤/中药复方/慢性低度炎症状态/肠道微生物Key words
polycystic ovary syndrome/insulin resistance/Qingfu Daotan Formula/Chinese herbal formulae/chronic low-grade inflammatory state/gut metabolism引用本文复制引用
王如烨,章勤,金晟玥,朱梦蕾,方晓红..清腑导痰汤改善多囊卵巢综合征伴胰岛素抵抗作用机制[J].中国中西医结合杂志,2025,45(4):462-474,13.基金项目
浙江省中医药管理局项目(No.2022ZB249) （No.2022ZB249）
浙江省中医药治疗妇科内分泌与代谢性疾病创新团队项目(No.2022SJCXTD) （No.2022SJCXTD）
2022年全国名老中医专家传承工作室建设项目(No.国中医药办人教函[2021]270号) （No.国中医药办人教函[2021]270号）
