Zhenzhu Tiaozhi Capsules Reduce Renal Lipid Deposition and Inflammation in Mouse Model of Diabetic Kidney Disease via SCAP-SREBP-1c/NLRP3 Signaling Pathway
10.13422/j.cnki.syfjx.20242036
- VernacularTitle:贞术调脂胶囊通过SCAP-SREBP-1c/NLRP3通路改善糖尿病肾病小鼠肾脏脂质沉积和炎症
- Author:
Tao ZHANG
1
;
Jie TAO
1
;
Yinghui ZHANG
1
;
Yiqi YANG
1
;
Xianglu RONG
1
;
Jiao GUO
1
Author Information
1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine， Guangdong Pharmaceutical University， Guangzhou 510006， China
- Publication Type:Journal Article
- Keywords:
Zhenzhu Tiaozhi capsules;
diabetic kidney disease;
sterol regulatory element-binding protein cleavage-activating protein （SCAP）-sterol regulatory element-binding protein-1c （SREBP-1c）/NOD-like receptor protein 3 （NLRP3） pathway;
lipid deposition;
inflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(13):114-121
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.
