Mitigation of Inflammatory Reaction of Diabetic Kidney Disease by Yizhiren (益智仁) Regulating NF-κB Pathway through Trimethylamine Oxide
Objective:To explore the mechanism of Yizhiren (益智仁) regulating NF-κB signaling pathway through trimethylamine oxide (TMAO) to alleviate inflammatory reaction of diabetic kidney disease (DKD).Methods:A total of 42 SPF-grade 4-week-old C57BK male mice were selected,of which 12 normal mice were randomly divided into a normal control group and a 0.2％ AMTO group,and 30 modeling mice were given a high-sugar and high-fat diet and were randomly divided into model control group,500 mg/kg and 100mg/kg Yizhiren groups,13 mg/kg canagliflozin group,and 1％ TAMO inhibitor group.After oral administration for continuously eight weeks,the body weight,blood glucose,24 h urine volume,24 h urinary albumin (UA),serum creatinine (SCR),blood urea nitrogen (BUN),urinary protein/creatinine ra-tio (ACR),TMAO,tumor necrosis factor-α (TNF-α),IL-1β,renal pathological tissue,and phosphorylated nuclear transcription factor-κB/nuclear transcription factor-κB (P-P65/P65) protein ratio were measured.Results:Compared with the normal control group,the body weight,blood glucose,24 h urine volume,the contents of 24 h UA,Scr,BUN,ACR,TMAO,TNF-α,and IL-1β,the ratio of P-P65/P65 pro-tein,and collagen deposition of mice in the model control group were significantly increased (P<0.01).The ratio of P-P65/P65 protein in the 0.2％ TMAO group was increased significantly (P<0.05).Compared with the model control group,24 h urine volume,the contents of Scr,ACR,and TAMO,collagen deposition,and P-P65/P65 protein ratio in the 500 and 100 mg/kg Yizhiren groups,13 mg/kg canagliflozin group,and 1％ TAMO inhibitor group were significantly decreased (P<0.01 or P<0.05).The 24 h UA was significantly decreased in the 500 and 100 mg/kg Yizhiren groups and 13 mg/kg canagliflozin group (P<0.01).The contents of BUN and TNF-α in the 500 mg/kg Yizhiren group,13 mg/kg canagliflozin group,and 1％ TAMO inhibitor group were significantly decreased (P<0.01 or P<0.05).The levels of IL-1β in the 500 mg/kg Yizhiren group and 1％ TAMO inhibitor group were significantly decreased (P<0.05).The correlation analysis showed that TMAO level was positively correlated with the levels of inflammatory cytokines TNF-α and IL-1β (P<0.01).Conclusion:Yizhiren can significantly improve renal function and inflammatory state in DKD mice,and the mechanism may be related to reducing TMAO levels and inhibiting the NF-κB signaling pathway.
NETL
NSTL
万方数据
