Panax notoginseng saponin R1 protects acute kidney injury by upregulating Wnt/β-catenin signaling pathway

Abstract

Objective: To observe the protective effect of Panax notoginseng saponin R1 (NTR1) on Acute Renal Injury (ARI) induced by sepsis and explore its possible mechanism. Methods: Male SD rats were randomly divided into 4 groups: Sham-operated group, Model control group, NTR1-treated group and CHIR-99021 (Wnt/β-catenin signaling pathway agonist)-treated group. The NTR1-treated group was given NTR1 at a dose of 20 mg/kg after the cecal ligation and perforation model was established, and the CHIR-99021-treated group was given CHIR-99021 at a dose of 30 mg/kg after the cecal ligation and perforation model was established, after 3, 6, 12, 24 and 48 hours, the blood and kidney were taken for follow-up experiment. The Model control group only received the same dose of saline as NTR1-treated and CHIR-99021-treated groups. In the Sham-operated group, the cecum was removed by laparotomy and then put back into the abdominal cavity. The pathological changes of renal tissue were observed at each time point, the serum levels of Creatinine (CRE), Urea Nitrogen (Bun), Neutrophil gelatinase-associated lipocalin (Ngal), Interleukin-6 (IL-6), Tumor Necrosis Factor (TNF-α) and Interleukin-1β (IL-1β) were measured. In addition, Western Blotting was used to detect the expression of GSK-3β protein in renal tissue at different time points. Results: Compared with Shame group, the glomerular structure of CLP Group was vacuolated and atrophied, and the glomerular damage of NTR1 and CHIR-99021 group was improved. The serum levels of CRE, Bun and Ngal in NTR1 group were significantly lower than those in model control group, and the serum levels of TNF-α, IL6, IL1-β and SOD in NTR1 group were significantly lower than those in model control group. Compared with the model group, the expression of GSK-3β protein in NTR1 group was decreased. Compared with model control group, the levels of BUN and Ngal in serum of CHIR-99021 group were significantly decreased, the expression of TNF-α, IL6, IL1-β and SOD in serum of CHIR-99021 group was significantly lower than that of model group, and the expression of GSK-3β in serum of CHIR-99021 group was significantly lower than that of model group. Conclusion: Both NTR1 and CHIR-99021 can alleviate the pathological changes, oxidative stress and inflammatory reaction in sepsis-induced ARI, the possible mechanism is related to the up-regulation of Wnt/β-catenin signaling pathway.