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
10.13422/j.cnki.syfjx.20251317
- VernacularTitle: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
- Author:
Ruijia LI
1
;
Zixuan WANG
1
;
Shilong GUO
1
;
Sen YANG
2
;
Jing LI
3
;
Qianqian ZHANG
3
;
Wen DONG
4
;
Dengzhou GUO
3
Author Information
1. Graduate School， Hebei University of Traditional Chinese Medicine， Shijiazhuang 050200， China
2. The Second Clinic of Hebei Provincial Directly Subordinate Organs， Shijiazhuang 050000， China
3. Hebei Provincial Hospital of Traditional Chinese Medicine， Shijiazhuang 050011， China
4. The First Hospital of Hebei Medical University， Shijiazhuang 050000， China
- Publication Type:Journal Article
- Keywords:
diabetic kidney disease;
db/db mice;
Danggui Shaoyaosan;
endoplasmic reticulum stress;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(6):28-35
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo 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. MethodsThirty 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. ResultsCompared 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 （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<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 （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS 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.
