Effect and Mechanism of Shuangshenling Granules on Chronic Renal Failure Rat Model
10.13422/j.cnki.syfjx.20250394
- VernacularTitle:双参苓颗粒对慢性肾衰竭大鼠模型的药效及作用机制
- Author:
Shuran LI
1
;
Yanying LI
2
;
Jingsheng ZHANG
1
;
Ronghua ZHAO
1
;
Shanshan GUO
1
;
Qiyue SUN
1
;
Zihan GENG
1
;
Lei BAO
1
;
Shuangrong GAO
1
;
Xiaolan CUI
1
;
Jing SUN
1
Author Information
1. Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100029，China
2. Beijing Increase Innovative Drug Co .Ltd.，Beijing 102200，China
- Publication Type:Journal Article
- Keywords:
Shuangshenling granules;
chronic kidney failure;
serum creatinine;
autophagy;
5/6 nephrectomy
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):46-55
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the pharmacological action and mechanism of Shuangshenling granules in treating chronic renal failure in rats，providing laboratory data to support clinical application of Shuangshenling granules. MethodSD rats （150-180 g），half males and half females in number，were used，with ten rats designated as the normal group，ten as the sham operation group，and the remaining rats undergoing chronic renal failure modeling induced by 5/6 nephrectomy. Two weeks after operation，serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured via orbital blood sampling to select successful model rats. Based on SCr values，the rats were evenly divided into the model group，Shenshuaining positive group （0.84 g·kg-1·d-1），and high，medium，and low dose groups of Shuangshenling granules （4.8，2.4，1.2 g·kg-1·d-1），with ten animals in each group. Each treatment group received drugs at 10 mL·kg-1 via intragastric administration once daily for six weeks. At 2，4，6 weeks after administration，SCr，BUN，24-hour urine volume，total urinary protein （UTP），urinary creatinine （UCr），creatinine clearance rate （CCr），serum albumin （SAlb），and total serum protein （STP） were measured. Following the experiment，kidney tissues were dissected for pathological examination. The expression levels of autophagy-related proteins，including PTEN-induced kinase 1 （PINK1），E3 ubiquitin-protein ligase parkin （Parkin），and microtubule-associated protein 1 light chain 3B （LC3B），were detected by immunofluorescence. ResultCompared with the normal group，the model group exhibited significantly increased levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.01），and decreased levels of SAlb and STP （P<0.01）. CCr showed an initial increase followed by a decrease. Histopathological results revealed glomerular hyperplasia and atrophy，with varying degrees of mesangial cell reduction，blood stasis in the glomeruli，and significant widening of Bowman's capsule. Visceral parietal layer cells were displaced or absent，leading to incomplete and damaged glomeruli. A large number of protein casts were present in the proximal and distal convoluted tubules，with reduced and displaced cells，swelling in some tubules，and interstitial inflammatory exudation predominantly comprising lymphocytes and a small number of neutrophils. Compared with the model group，all dose groups of Shuangshenling granules significantly reduced levels of SCr，BUN，24-hour urine volume，UTP，and UCr （P<0.05，P<0.01） and increased SAlb and STP levels （P<0.01） at 2，4，and 6 weeks after administration. The three dose groups also improved CCr and alleviated renal pathological injury in varying degrees at 2-6 weeks after administration. Immunofluorescence results showed that the expression levels of PINK1，Parkin，and LC3B were significantly reduced in the model group compared with the normal group，whereas all dose groups of Shuangshenling granules significantly upregulated the expression levels of PINK1，Parkin，and LC3B compared with the model group. ConclusionShuangshenling granules significantly improved renal function and pathological injury in rats with chronic renal failure，likely through the upregulation of PINK1-mediated autophagy.
