Renal Protection Mechanism of Jasminoidin in Metabolic Syndrome Rat Reduced by Fructose Based on the TLR4-TBK1-IKKε Signal Pathway

OBJECTIVE To investigate the renal protective effects of jasminoidin on the rats with metabolic syndrome induced by fructose. METHODS 50 male SD rats were randomly divided into normal group， model group， jasminoidin group (30， 60 mg/kg) and allopurinol group (10 mg/kg)， each of 10. The renal injury model in rats with metabolic syndrome was built by 10% fructose. After 8 weeks， the animals were killed. Insulin tolerance tests (ITT)， serum uric acid， creatinine， triglyceride (TG) and total cholesterol (TC)， interleukin-1β (IL-1β)， IL-6 and tumor necrosis factor-α (TNF-α)， urine uric acid， creatinine levels， and renal TG， TC， IL-1β， IL-6 and TNF-α levels were measured. In addition， the changes of nuclear transcription factor-κB (NF-κB) and Toll-like receptor 4 (TLR4)- TANK-binding kinase 1 (TBK1)-IκB kinase ε (IKKε) signaling pathway in the renal tissue were examined. RESULTS Jasminoidin significantly improved insulin resistance， decreased serum uric acid， creatinine， creatinine， TG， TC， IL-1β， IL-6 and TNF-α levels， and significantly increased urine uric acid and creatinine levels， with reduction of TG， TC， IL-1β， IL-6 and TNF-α in the kidney. Jasminoidin also significantly inhibited NF-κB and TLR4-TBK1-IKKε signal pathway. At the same time， it was further confirmed that fructose stimulation induced the increased expression of inflammatory factors and the activation of TLR4-TBK1-IKKε signaling pathway in human renal proximal tubule epithelial cell line HK-2， and jasminoidin and TLR4 inhibitor TAK-242 significantly improved the abnormal expression of the above index. CONCLUSION The renal protective effects of jasminoidin on the rats with hyperuricemia， lipid accumulation and renal inflammation induced by fructose may be related to its inhibition of TLR4-TBK1-IKKε signal pathway.