Regulatory effect of TAK1 inhibitors on MAPK and NF-κB signaling pathway in diabetic rats and its renal protection mechanism / 中国比较医学杂志

ABSTRACT

Objective To explore the regulatory effect of TAK 1 inhibitors on MAPK and NF-κB signaling pathway in diabetic rats and its renal protection mechanism .Methods A total of 48 rats accorded to the random number table method were divided into DN group , TAK1 group and control group ,each group with 16 rats,control group with normal fed , DN group and TAK1 group by the intraperitoneal injection of 1%50 mg/kg STZ DN model rat.8 rats were killed in each group at 4 weeks and 8 weeks respectively ,the pathological changes of renal tissue were observed ,serum TNF-α,MCP-1,IL-1βlevels were detected by enzyme linked immunosorbent assay ,p38MAPK,NF-κBp63 protein expression were detected by Western blotting ,p38MAPK、NF-κBp63 mRNA levels in renal tissue were detected by real time fluorescence quantitative PCR.Results At 4 weeks and 8 weeks, the body weight, blood glucose and UAER of DN group and TAKl group were significantly higher than those in control group (P <0.05).The body weight and UAER of DN group were significantly higher than those of TAK1 group (P <0.05).The serum TNF-α,MCP-1,IL-1βlevels in DN group and TAK1 group were significantly higher than those in control group (P <0.05),and DN group serum TNF-α,MCP-1,IL-1βlevels were significantly higher than those in TAK1 group (P <0.05).The expression levels of p38MAPK,NF-κBp63 protein and mRNA in DN group, TAK1 group were significantly higher than those in control group (P <0.05), and p38MAPK,NF-κBp63 protein and mRNA in DN group was significantly higher than that in TAK 1 group ( P <0.05 ) .Conclusions TAK1 induces inflammation by activating MAPK and NF-κB signaling pathways,and participates in diabetic renal injury . TAK1 inhibitors with anti-inflammatory effect by down regulate the expression of inflammatory factors .