Exploration on the diuretic mechanism of Zhuling Decoction on ADRN mice from CDK18/STUB1/AQP2 pathway
10.3760/cma.j.cn115398-20240802-00012
- VernacularTitle:基于CDK18/STUB1/AQP2通路探讨猪苓汤对阿霉素肾病小鼠的利尿作用机制
- Author:
Wenfeng XU
1
;
Fan WU
;
Yajun PENG
;
Qun TANG
;
Xuhua LI
;
Hua HU
Author Information
1. 湖南中医药大学第一附属医院肾脏内科，长沙 410007
- Keywords:
Zhu Ling Tang;
Nephrotic syndrome;
Edema;
Cyclin-Dependent Kinases;
STIP1 homology and U-box protein 1;
Aquaporin 2;
Mice
- From:
International Journal of Traditional Chinese Medicine
2025;47(5):624-629
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the diuretic effects of Zhuling Decoction on mice with adriamycin nephropathy (ADRN); To explore its mechanism.Methods:Totally 32 SPF male C57BL/6 mice were divided into a blank group of 7 mice and a model group of 25 mice using a random number table method. ADRN model was prepared by single tail vein injection of 0.01 g/kg of amphotericin. Two weeks later, the successfully modeled mice were divided into a model group (7 mice), a furosemide group (8 mice), and a Zhuling Decoction group (8 mice). The blank group and model group mice were given equal volumes of injection water by gavage. The furosemide group was given 2.6 mg/kg of furosemide by gavage, and the Zhuling Decoction group was given 6.5 g/kg of Zhuling Decoction by gavage, once a day, for 8 consecutive weeks. Changes in body weight and urine output of mice were observed. A biochemical analyzer was used to detect 24-hour urinary protein quantification and blood potassium and SCr levels in mice. HE staining was used to observe pathological changes in mouse kidneys, and immunohistochemistry and Western blot were used to detect the homology of cyclin dependent kinase 18 (CDK18), STIP1, and the expressions of U-box protein 1 (STUB1) and aquaporin 2 (AQP2) in mouse kidney tissue cells.Results:Compared with the model group, both the furosemide and Zhuling Decoction groups exhibited increased 24-hour urine output ( P<0.05); compared with the model group and furosemide group, Zhuling Decoction group showed reduced average optical density values and protein expressions of CDK18 and AQP2 ( P<0.05) and increased STUB1 average optical density value and protein expression ( P<0.05). Conclusion:Zhuling Decoction can increase 24-hour urine output in ADRN mice, and the mechanism may be related to down-regulation of CDK18 and AQP2 protein expressions and up-regulation of STUB1 protein expression, thereby modulating the CDK18/STUB1/AQP2 pathway and reducing water reabsorption.
