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Mechanism of
Yishen Quzhuo Decoction in repairing intestinal barrier in obese rats with polycystic ovary syndrome based on MAPK/JNK signaling pathway- Beijing Journal of Traditional Chinese Medicine Vol. 44, Issue 5, Pages: 584-592(2025)
- 作者机构：
1.首都医科大学附属北京中医医院妇科，北京 100010
2.首都医科大学中医药临床医学院，北京 100010
3.首都医科大学附属北京中医医院超声科，北京 100010
- 作者简介：
- 基金信息：
DOI：10.16025/j.1674-1307.2025.05.009
CLC：Received：26 April 2024，
Published：25 May 2025
- 稿件说明：
移动端阅览
高征，李梦元，梁婧翘，等.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.
GAO Zheng,LI Mengyuan,LIANG Jingqiao,et al.Mechanism of Yishen Quzhuo Decoction in repairing intestinal barrier in obese rats with polycystic ovary syndrome based on MAPK/JNK signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(05):584-592.
高征，李梦元，梁婧翘，等.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. DOI： 10.16025/j.1674-1307.2025.05.009.
GAO Zheng,LI Mengyuan,LIANG Jingqiao,et al.Mechanism of Yishen Quzhuo Decoction in repairing intestinal barrier in obese rats with polycystic ovary syndrome based on MAPK/JNK signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(05):584-592. DOI： 10.16025/j.1674-1307.2025.05.009.
摘要
目的
2
探讨益肾祛浊方通过调控丝裂原活化蛋白激酶（MAPK）/Jun激酶（JNK）信号通路对肥胖型多囊卵巢综合征（PCOS）模型大鼠肠道屏障修复的作用机制。
方法
2
将32只大鼠随机分为空白组、模型组、益肾祛浊方（中药）组、二甲双胍（对照）组，每组8只。空白组给予普通饲料，其余各组均以来曲唑灌胃联合高脂饲料喂养建立肥胖型PCOS大鼠模型。中药组大鼠给予10 g/kg益肾祛浊方药液灌胃，对照组大鼠给予二甲双胍50 mg/kg灌胃，空白组、模型组大鼠给予0.9%氯化钠溶液10 g/kg灌胃，均每天1次，连续干预14 d。酶联免疫吸附试验（ELISA）检测大鼠血清中肠型脂肪酸结合蛋白（I-FABP）、内毒素（LPS）、D-乳酸（D-lac）水平，苏木精-伊红（HE）染色法观察回肠组织病理变化，免疫组化法检测大鼠回肠组织连蛋白（Zonulin）、紧密连接蛋白1（ZO-1）、脂多糖结合蛋白（LBP）、JNK及磷酸化JNK（p-JNK）表达，Western Blotting法检测大鼠回肠组织Zonulin、ZO-1、LBP、JNK、p-JNK蛋白表达。
结果
2
与空白组比较，模型组大鼠血清I-FABP、D-lac、LPS水平高（
P
<
0.01）；回肠组织切片肠黏膜层上皮细胞局部脱落，黏膜层不完整，杯状细胞数量减少，可见炎症细胞弥漫性浸润；Zonulin、LBP蛋白表达高（
P
<
0.01），ZO-1蛋白表达低（
P
<
0.05）；p-JNK蛋白表达高（
P
<
0.01）。与模型组比较，中药组血清I-FABP、D-lac、LPS水平低（
P
<
0.01）；回肠黏膜层上皮细胞完整、排列整齐，杯状细胞数量有所增加，淋巴细胞明显减少；Zonulin、LBP蛋白表达低（
P
<
0.05），ZO-1蛋白表达高（
P
<
0.05），p-JNK蛋白表达低（
P
<
0.01）。且中药组以上指标变化优于对照组。
结论
2
益肾祛浊方可能通过调控MAPK/JNK信号通路，调节循环LPS水平及回肠组织紧密连接结构，从而修复肥胖型PCOS模型大鼠肠道屏障。
Abstract
Objective
2
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
2
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 imm
unosorbent 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
2
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
2
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
Keywords
references
SADEGHI HM , ADELI I , CALINA D , et al . Polycystic ovary syndrome:a comprehensive review of pathogenesis,management,and drug repurposing [J ] . Int J Mol Sci , 2022 , 23 ( 2 ): 583 .
ZHANG J , XING C , CHENG X , et al . Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome:a single-center,open-labeled prospective randomized controlled trial [J ] . Front Endocrinol (Lausanne) , 2022 , 13 : 1003238 .
蔡云 , 许昕 . 益肾祛浊方对PCOS模型大鼠胰岛素抵抗及性激素的影响 [J ] . 环球中医药 , 2017 , 10 ( 6 ): 650 - 654 .
张晓丹 , 蔡云 , 许昕 . 益肾祛浊方对PCOS-IR大鼠Ghrelin、SHBG及VF的影响 [J ] . 中国医药导报 , 2017 , 14 ( 33 ): 9 - 12,21 .
尹谦 , 李美和 , 梁婧翘 , 等 . 益肾祛浊方调节雌激素通路干预PCOS-IR大鼠脂代谢异常的研究 [J ] . 中华中医药杂志 , 2023 , 38 ( 7 ): 3329 - 3333 .
尹谦 , 王明星 , 许昕 . 益肾祛浊方对多囊卵巢综合征胰岛素抵抗模型大鼠激素受体表达的干预作用 [J ] . 世界中医药 , 2020 , 15 ( 6 ): 836 - 841 .
尹谦 . 益肾祛浊方对PCOS-IR慢性炎症状态及Kiss1/GPR54信号影响的机制研究 [D ] . 北京 : 首都医科大学 , 2023 .
PARKER J , O'BRIEN C , HAWRELAK J . A narrative review of the role of gastrointestinal dysbiosis in the pathogenesis of polycystic ovary syndrome [J ] . Obstet Gynecol Sci , 2022 , 65 ( 1 ): 14 - 28 .
FANG JY , RICHARDSON BC . The MAPK signalling pathways and colorectal cancer [J ] . Lancet Oncol , 2005 , 6 ( 5 ): 322 - 327 .
AL-SADI R , YE D , SAID HM , et al . Cellular and molecular mechanism of interleukin-1β modulation of Caco-2 intestinal epithelial tight junction barrier [J ] . J Cell Mol Med , 2011 , 15 ( 4 ): 970 - 982 .
AL-SADI R , GUO S , YE D , et al . TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1 [J ] . Am J Pathol , 2013 , 183 ( 6 ): 1871 - 1884 .
RAN X , LI Y , CHEN G , et al . Farrerol ameliorates TNBS-induced colonic inflammation by inhibiting ERK1/2,JNK1/2,and NF-κB signaling pathway [J ] . Int J Mol Sci , 2018 , 19 ( 7 ): 2037 .
苗明三 , 闫晓丽 , 方晓艳 , 等 . 多囊卵巢综合征动物模型制备规范(草案) [J ] . 中华中医药杂志 , 2019 , 34 ( 6 ): 2576 - 2579 .
蔡云 , 许昕 . 来曲唑联合高脂饲料建立PCOS-IR大鼠模型实验研究 [J ] . 首都医科大学学报 , 2017 , 38 ( 2 ): 244 - 248 .
乔杰 , 李蓉 , 李莉 , 等 . 多囊卵巢综合征流行病学研究 [J ] . 中国实用妇科与产科杂志 , 2013 , 29 ( 11 ): 849 - 852 .
郭浩洋 , 张思琪 , 王丽娜 , 等 . 多囊卵巢综合征伴胰岛素抵抗排卵障碍中西医综合分析 [J ] . 辽宁中医药大学学报 , 2023 , 25 ( 2 ): 197 - 200 .
TEEDE HJ , TAY CT , LAVEN JJE , et al . Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome [J ] . Fertil Steril , 2023 , 120 ( 4 ): 767 - 793 .
SHARPE A , MORLEY LC , TANG T , et al . Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome [J ] . Cochrane Database Syst Rev , 2019 , 12 ( 12 ): Cd013505 .
孟蕾 , 宋维鹏 , 刘秀娟 , 等 . 脓毒症预后不良患者血清I-FABP、DAO、D-Lac水平变化及其危险因素探讨 [J ] . 分子诊断与治疗杂志 , 2023 , 15 ( 2 ): 265 - 268,272 .
AISEMBERG J , C-AVERCELLI , M-VBARIANI , et al . Progesterone is essential for protecting against LPS-induced pregnancy loss.LIF as a potential mediator of the anti-inflammatory effect of progesterone [J ] . PLoS One , 2013 , 8 ( 2 ): 56161 .
KABAKCHIEVA P , GATEVA A , VELIKOVA T , et al . Meteorin-like protein and Zonulin in polycystic ovary syndrome:exploring associations with obesity,metabolic parameters,and inflammation [J ] . Biomedicines , 2024 , 12 ( 1 ): 222 .
MARTEL J , CHANG SH , KO YF , et al . Gut barrier disruption and chronic disease [J ] . Trends Endocrinol Metab , 2022 , 33 ( 4 ): 247 - 265 .
KEITA AV , SÖDERHOLM JD . The intestinal barrier and its regulation by neuroimmune factors [J ] . Neurogastroenterol Motil , 2010 , 22 ( 7 ): 718 - 733 .
ALIZADEH A , AKBARI P , GARSSEN J , et al . Epithelial integrity,junctional complexes,and biomarkers associated with intestinal functions [J ] . Tissue Barriers , 2022 , 10 ( 3 ): 1996830 .
DAMMS-MACHADO A , LOUIS S , SCHNITZER A , et al . Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction [J ] . Am J Clin Nutr , 2017 , 105 ( 1 ): 127 - 135 .
SHEN L , ZHOU Y , WU X , et al . TREM1 blockade ameliorates lipopolysaccharide-induced acute intestinal dysfunction through inhibiting intestinal apoptosis and inflammation response [J ] . Biomed Res Int , 2021 , 16 : 6635452 .
SHEHATA MF . Important genetic checkpoints for insulin resistance in salt-sensitive (S) Dahl rats [J ] . Cardiovasc Diabetol , 2008 , 7 : 19 .
LIANG Z , YUAN Z , GUO J , et al . Ganoderma lucidum polysaccharides prevent palmitic acid-evoked apoptosis and autophagy in intestinal porcine epithelial cell line via restoration of mitochondrial function and regulation of MAPK and AMPK/Akt/mTOR signaling pathway [J ] . Int J Mol Sci , 2019 , 20 ( 3 ): 478 .
ZHANG Y , WU S , MA J , et al . Bacterial protein AvrA stabilizes intestinal epithelial tight junctions via blockage of the C-Jun N-terminal kinase pathway [J ] . Tissue Barriers , 2015 , 3 ( 1-2 ): 972849 .
李美和 . 基于益肾祛浊方影响雌激素信号通路及PM20D1改善PCOS-IR代谢异常的机制研究 [D ] . 北京 : 首都医科大学 , 2022 .
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