OBJECTIVE To explore the protective effect of Jianpi Shengqing Jiangzhuo Recipe on db/db mice with diabetic kidney disease (DKD) and its possible mechanism.

METHODS Thirty-two 8-week-old male db/db mice were randomly divided into four groups (n=8), including the model group, the Western medicine group Dapagliflozin (1.0 mg · kg^-1·d^-1), low-dose Jianpi Shengqing Jiangzhuo group (19.63 g · kg^-1 ·d^-1), and high-dose Jianpi Shengqing Jiangzhuo group (58.89 g · kg^-1·d^-1). Additionally, 8 db/m mice were used as the normal group. The mice were orally administered once a day for 10 consecutive weeks. The general survival status of the mice was observed, and the body weight, fasting blood glucose (FBG), and urine volume of the mice were dynamically monitored; urine creatinine and urine microalbumin were detected, and urine microalbumin excretion (UAE) and protein-creatinine ratio (ACR) were calculated. After the last intervention, mice were fasted for 12 h, blood was collected under anesthesia, and kidney tissue was separated; blood creatinine (Scr), serum urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were tested; HE and Masson staining were used to observe pathological changes in renal tissue; Oil Red O staining was used to observe the deposition of lipid droplets in the kidneys, and Image J was used for quantitative analysis; ELISA was used to detect the levels of TNF-α and IL-1β in renal tissue; Western blot was used to detect the expression of SIRT1, SREBP-1, and PPAR-α proteins in renal tissue.

RESULTS Compared with the normal group mice, the body weight, FBG, Scr, TG, TC, HDL-C, LDL-C, urine volume, UAE, and ACR of the model group mice were significantly increased (P < 0.05, P < 0.01); the glomerular volume was significantly increased, renal fibrosis was altered, and renal lipid droplet deposition increased (P < 0.01); renal TNF-α, IL-1β, SREBP-1 expression increased (P < 0.01), and SIRT1 and PPAR-α expression decreased (P < 0.01). Compared with the model group, the FBG levels in the Western medicine group was significantly decreased at the 5th and 10th weeks of intervention (P < 0.05, P < 0.01); after the intervention, the Scr, UAE and ACR in the Western medicine group and high-dose Jianpi Shengqing Jiangzhuo group were significantly decreased (P < 0.05, P < 0.01), and the serum TG level in the high-dose Jianpi Shengqing Jiangzhuo group was also significantly decreased (P < 0.01); the Western medicine group and the high-dose group of Jianpi Shengqing Jiangzhuo group improved renal pathological changes and lipid deposition (P < 0.05, P < 0.01), with decreased levels of TNF-α and IL-1β and increased expression of SIRT1 and PPAR-α proteins (P < 0.05, P < 0.01); high-dose group of Jianpi Shengqing Jiangzhuo decreased the expression of SREBP-1 (P < 0.01).

CONCLUSION Jianpi Shengqing Jiangzhuo Recipe can improve proteinuria, kidney injury, renal lipid deposition as well as inflammatory reaction in DKD, which may be related to the activation of the SIRT1/SREBP-1/PPAR-α pathway to regulate lipid homeostasis.