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

高征; 李梦元; 梁婧翘; 张雅冬; 许昕

doi:10.16025/j.1674-1307.2025.05.009

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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

实验研究 | 更新时间：2025-07-07

- 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
- 北京中医药 2025年44卷第5期页码：584-592
- 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：
  
  高征，女，37岁，博士，主治医师。研究方向：多囊卵巢综合征的中西医结合治疗。
  许昕，E-mail：xuixn@bjzhongyi.com
- 基金信息：
  
  国家自然科学基金资助项目(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)
- DOI：10.16025/j.1674-1307.2025.05.009
  中图分类号：
- 收稿日期：2024-04-26，
  
  纸质出版日期：2025-05-25
- 稿件说明：
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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

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

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

与空白组比较，模型组大鼠血清I-FABP、D-lac、LPS水平高（

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（

0.01），ZO-1蛋白表达低（

0.05）；p-JNK蛋白表达高（

0.01）。与模型组比较，中药组血清I-FABP、D-lac、LPS水平低（

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（

0.05），ZO-1蛋白表达高（

0.05），p-JNK蛋白表达低（

0.01）。且中药组以上指标变化优于对照组。

结论

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

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 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

Compared with the blank group， the model group exhibited significantly elevated serum levels of I-FABP， D-lac， and LPS （

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 （

0.01）， while ZO-1 expression was significantly decreased （

0.05）， and p-JNK expression was also significantly elevated （

0.01）. Compared with the model group， the Chinese medicine group showed significantly reduced serum levels of I-FABP， D-lac， and LPS （

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 （

0.05）， ZO-1 expression was significantly increased （

0.05）， and p-JNK expression was significantly decreased （

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

Keywords

references

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