北京中医药2025，Vol.44Issue(5)：584-592,9.DOI:10.16025/j.1674-1307.2025.05.009
基于MAPK/JNK信号通路研究益肾祛浊方修复肥胖型多囊卵巢综合征大鼠肠道屏障的作用机制
Mechanism of Yishen Quzhuo Decoction in repairing intestinal barrier in obese rats with polycystic ovary syndrome based on MAPK/JNK signaling pathway
摘要
Abstract
Objective To investigate the mechanism by which Yishen Quzhuo Decoction repairs the intestinal barrier in obese polycystic ovary syndrome(PCOS)model rats by regulating the mitogen-activated protein kinase(MAPK)/c-Jun N-terminal kinase(JNK)signaling pathway.Methods Thirty-two rats were randomly divided into four groups(n=8 per group):blank group,model group,Yishen Quzhuo Decoction(Chinese medicine)group,and metformin(control)group.Rats in the blank group were fed a standard diet,while the other groups received high-fat diets combined with intragastric administration of letrozole to establish an obese PCOS model.Rats in the Chinese medicine group were administered Yishen Quzhuo Decoction at 10 g/kg by gavage.The control group received metformin at 50 mg/kg.The blank and model groups were given 0.9%sodium chloride solution at 10 g/kg.All interventions were administered once daily for 14 consecutive days.Serum levels of intestinal fatty acid-binding protein(I-FABP),lipopolysaccharide(LPS),and D-lactic acid(D-lac)were measured by enzyme-linked immunosorbent assay(ELISA).Histopathological changes in the ileum were observed using hematoxylin and eosin(HE)staining.Expression levels of Zonulin,tight junction protein-1(ZO-1),lipopolysaccharide-binding protein(LBP),JNK,and phosphorylated JNK(p-JNK)in ileal tissues were detected using immunohistochemistry and Western blot.Results Compared with the blank group,the model group exhibited significantly elevated serum levels of I-FABP,D-lac,and LPS(P<0.01).Ileal tissue sections revealed localized shedding of intestinal mucosal epithelial cells,an incomplete mucosal layer,reduced goblet cell numbers,and diffuse infiltration of inflammatory cells.Protein expression levels of Zonulin and LBP were significantly increased(P<0.01),while ZO-1 expression was significantly decreased(P<0.05),and p-JNK expression was also significantly elevated(P<0.01).Compared with the model group,the Chinese medicine group showed significantly reduced serum levels of I-FABP,D-lac,and LPS(P<0.01).The intestinal mucosal epithelial cells were intact and well-organized,goblet cell numbers increased,and lymphocyte infiltration was markedly reduced.Protein expression levels of Zonulin and LBP were significantly decreased(P<0.05),ZO-1 expression was significantly increased(P<0.05),and p-JNK expression was significantly decreased(P<0.01).These improvements in the Chinese medicine group were superior to those observed in the metformin group.Conclusion Yishen Quzhuo Decoction may repair the intestinal barrier in obese PCOS model rats by regulating the MAPK/JNK signaling pathway,thereby modulating circulating LPS levels and enhancing the tight junction structure of ileal tissue.关键词
多囊卵巢综合征/肥胖/益肾祛浊方/肠道屏障/丝裂原活化蛋白激酶/Jun激酶信号通路Key words
polycystic ovary syndrome(PCOS)/obesity/Yishen Quzhuo Decoction/intestinal barrier/MAPK/JNK signaling pathway引用本文复制引用
高征,李梦元,梁婧翘,张雅冬,许昕..基于MAPK/JNK信号通路研究益肾祛浊方修复肥胖型多囊卵巢综合征大鼠肠道屏障的作用机制[J].北京中医药,2025,44(5):584-592,9.基金项目
国家自然科学基金资助项目(81674010) （81674010）
全国名老中医药专家传承工作室建设项目(国中医办人教函[2021]270号) （国中医办人教函[2021]270号）
