【摘要】 目的探讨TAK1抑制剂对糖尿病大鼠MAPK及NF-κB信号通路的影响及其对肾脏的保护机制。方法将48只大鼠按照随机数字表法分为DN组、TAK1组和对照组,每组16只。对照组大鼠正常喂养,不做任何处理;DN组、TAK1组通过向大鼠腹腔注射1%50 mg/kg STZ建立DN大鼠模型。每组分别于4周、8周时处死8只大鼠,观察各组大鼠肾脏组织病理变化,检测血清TNF-α、MCP-1、IL-1β表达,肾脏组织p38MAPK、NF-κBp63蛋白表达及p38MAPK、NF-κBp63 mRNA表达。结果 4周、8周时,DN组、TAK1组大鼠体质量、血糖、UAER均显著高于对照组(P<0.05),DN组大鼠体质量、UAER显著高于TAK1组(P<0.05)。DN组、TAK1组血清TNF-α、MCP-1、IL-1β水平显著高于对照组(P<0.05),DN组大鼠上述指标高于TAK1组(P<0.05);DN组、TAK1组p38MAPK、NF-κBp63蛋白及mRNA表达水平显著高于对照组(P<0.05),其中DN组上述指标高于TAK1组(P<0.05)。结论 TAK1通过激活MAPK及NF-κB信号通路来诱导炎症反应,并参与糖尿病肾脏损伤;TAK1抑制剂能够下调炎症因子的表达和释放而发挥抗炎作用。更多还原

【Abstract】 Objective To explore the regulatory effect of TAK1 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-1β levels were detected by enzyme linked immunosorbent assay,p38 MAPK,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-1β levels 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-1β levels weresignificantly higher than those in TAK1 group(P < 0.05).The expression levels of p38 MAPK,NF-κBp63 protein and mRNA in DN group,TAK1 group were significantly higher than those in control group(P < 0.05),and p38 MAPK,NF-κBp63 protein and mRNA in DN group was significantly higher than that in TAK1 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.更多还原