Abstract
OBJECTIVES: To investigate the therapeutic effect of Jia Wei Qingxin Lotus Seed Drink (QISD) on renal injury in mice with diabetic kidney disease (DKD) and its mechanism. METHODS: The immunogenes differentially expressed in renal tubular epithelial cells (HK-2) induced by late glycosylation end products were screened using GSE193192 dataset from GEO database and the pharmacological mechanisms were predicted. Male ICR mouse models of DKD established by high-fat feeding for 4 weeks and intraperitoneal streptozotocin injection for 5 days were randomized for treatment with low (14.46 g/kg), medium (28.92 g/kg) and high (57.84 g/kg) doses of QISD via gavage for 12 weeks, with dapagliflozin as the positive control drug (n=8). Penal pathologies of the mice were observed by HE, PAS and Masson staining, and renal expression levels of KDM3C, SP1, TNF-α, and MCP-1 mRNAs and proteins were detected using RT-qPCR and Western blotting. In a HK-2 cell model of lipopolysaccharide (LPS)-induced inflammatory injury, the effects of small-molecule inhibitors were tested to explore the therapeutic mechanism of QISD against cell inflammation. RESULTS: QISD treatment significantly lowered serum levels of glycated serum protein, creatinine and urea nitrogen, reduced glycogen accumulation, attenuated glomerular hypertrophy, and decreased renal inflammatory infiltration in DKD mouse models. QISD also reduces the expression levels of KDM3C, SP1, TNF‑α and MCP-1 in the kidney tissues of the mice. In LPS-induced HK-2 cells, the application of JIB-04, an inhibitor of KDM3C, obviously suppressed the expression levels of the inflammatory factors including TNF‑α, MCP-1 and ICAM-1. CONCLUSIONS: QISD can ameliorate renal injury in DKD mice by inhibiting inflammatory response via suppressing excessive activation of the KDM3C/SP1 signaling pathway.