Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells

LI Ruijia; WANG Zixuan; GUO Shilong; YANG Sen; LI Jing; ZHANG Qianqian; DONG Wen; GUO Dengzhou

doi:10.13422/j.cnki.syfjx.20251317

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Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells

更新时间：2026-02-28

- Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 6, Pages: 28-35(2026)
- 作者机构：
  
  1.河北中医药大学研究生学院，石家庄 050200
  2.河北省中医院，石家庄 050011
  3.河北省直属机关第二门诊部，石家庄 050000
  4.河北医科大学第一医院，石家庄 050000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20251317
  CLC： R587.1;R285;R289
- Received：18 June 2025，
  
  Revised：2025-09-29，
  
  Accepted：11 October 2025，
  
  Online First：14 October 2025，
  
  Published：20 March 2026
- 稿件说明：
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李睿嘉,王子轩,郭世龙等.基于肾小球内皮细胞内质网应激探索当归芍药散对db/db小鼠糖尿病肾病的保护作用及机制[J].中国实验方剂学杂志,2026,32(06):28-35.

LI Ruijia,WANG Zixuan,GUO Shilong,et al.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):28-35.
李睿嘉,王子轩,郭世龙等.基于肾小球内皮细胞内质网应激探索当归芍药散对db/db小鼠糖尿病肾病的保护作用及机制[J].中国实验方剂学杂志,2026,32(06):28-35. DOI： 10.13422/j.cnki.syfjx.20251317.

LI Ruijia,WANG Zixuan,GUO Shilong,et al.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(06):28-35. DOI： 10.13422/j.cnki.syfjx.20251317.

摘要

目的

探讨当归芍药散（DSS）干预db/db小鼠肾损害的疗效，并探究其对肾组织内质网应激（ERS）的影响。

方法

选取8周龄雄性db/db小鼠30只和db/m小鼠6只，适应饲养1周后，监测尿微量白蛋白和血糖，建立糖尿病肾病（DKD）模型。模型小鼠随机分为模型组，厄贝沙坦组和DSS低、中、高剂量组（16.77、33.54、67.08 g·kg

-1

·d

-1

），另设正常组进行对照，各组灌胃相应药物或生理盐水8周。干预结束后，观察小鼠一般情况，检测血胱抑素-C（Cys-C）、24 h尿总蛋白总量（24 h-UTP）、24 h尿微量白蛋白（24 h-UMA）、尿肌酐（Ucr）、尿素氮（UUN），透射电镜观察肾小球基底膜（GBM）、肾小球内皮细胞内质网超微结构。蛋白免疫印迹法（Western blot）、实时荧光定量聚合酶链式反应（Real-tmie PCR）和免疫组化分析肾组织结构及葡萄糖调节蛋白78（GRP78）、C/EBP同源蛋白（CHOP）等表达。

结果

与正常组小鼠比较，模型组小鼠表现蜷缩、反应迟钝、被毛枯槁，Cys-C、24 h-UTP、24 h-UMA、UUN升高（

0.05），Ucr下降（

0.05）。GBM显著增厚，足细胞足突融合。GRP78、CHOP、ATF6蛋白表达均显著升高（

0.05），GRP78、CHOP mRNA表达增加（

0.05），免疫组化显示GRP78信号显著增强（

0.05）；用药后小鼠行为改善，GBM及足细胞结构恢复正常，ER形态改善，生化指标显著好转。Western blot、Real-tmie PCR和免疫组化检测显示，DSS干预组ERS相关指标表达下降（

0.05），提示ERS缓解，肾功能改善。

结论

DSS可有效缓解db/db小鼠肾组织病理损伤，该作用可能与调控肾小球内皮细胞的ERS有关，但具体信号机制仍需后续研究阐明。

Abstract

Objective

To investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues.

Methods

Thirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg

-1

·d

-1

）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers.

Results

Compared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （

0.05）， while Ucr decreased （

0.05）. The GBM was significantly th

ickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （

0.05）， the mRNA levels of GRP78 and CHOP increased （

0.05）， and immunohistochemistry showed an enhanced GRP78 signal （

0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （

0.05）， suggesting alleviated ERS and improved renal function.

Conclusion

DSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

关键词

Keywords

references

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