摘要
目的探讨Toll样受体-4(TLR-4)的选择性抑制剂TAK-242对糖尿病大鼠肾脏的保护作用及可能机制。方法健康雄性SD大鼠60只,随机分为正常对照(NC)组、DN模型(M)组及TAK-242治疗(TAK-242)组。腹腔一次性注射STZ(60mg/kg)建立DN大鼠模型。造模成功后4和8周测定体重、血糖、24小时尿蛋白、血肌酐(Scr)、血浆白蛋白水平,8周末取新鲜肾组织检测人核因子κB抑制蛋白α(IκBα)、核转因子p65(NF-KBP65)、TNF-α和单核细胞趋化蛋白-1(MCP-1)的表达量。结果与NC组相比,M和TAK-242组血糖、Scr、尿蛋白水平均升高(P<0.05),体重、血浆白蛋白的水平降低(P<0.05);与M组相比,TAK-242可减少Scr[(69.8±7.96)μmol/L]、尿蛋白[(35.21±8.06)mg/d]含量(P<0.05),增加血浆白蛋白[(28.1±6.9)g/L]含量(P<0.05);与M组相比,TAK-242可减轻DN大鼠肾脏组织中核内NF-KBP65含量,以及TNF-α和MCP-1的表达,抑制IκBα的降解(P<0.05)。结论 TAK-242对DN大鼠有保护作用,其机制可能与抑制NF-κB信号通路相关。
Objective To explore the protective effect of TAK-242,a selective inhibitor of toll-like receptor 4（TLR4）,on kidney in diabetic rats and its possible mechanism. Methods A total of 60 healthy male SD rats were selected and randomly divided into three groups：normal control group（NC,n=20）,diabetic nephropathy model group（M,n=20）and TAK-242 treatment group（TAK-242,n=20）.The diabetic nephropathy rat model was established by one time injection of 60 mg/kg streptozotocin intraperitoneally.Body weight,blood glucose,24-hour urine protein,serum creatinine（Scr）and plasma albumin were measured at 4and 8weeks after modeling.Protein expression levels of human nuclear factorκb inhibitor proteinα（IκBα）,NF-KBP65,TNF-αand monocyte chemoattractant protein 1（MCP-1）were detected in fresh kidney tissue at the end of 8 weeks. Results Blood glucose,Scr and 24-hour urine protein were significantly higher while body weight and plasma albumin were significantly lower in M and TAK-242 groups than in NC group（P〈0.05）.Scr（69.8±7.96）μmol/L and 24-hour urine protein（35.21±8.06）mg/d were significantly lower and plasma albumin level（28.1±6.9）g/L was significantly higher in TAK-242 group than in M group（P〈0.05）.The content of NF-KBP65 and expression levels of TNF-αand MCP-1 were significantly lower while IκBαlevel was higher in TAK-242 group than in M group（P〈0.05）. Conclusion TAK-242 can protect the kidney in rats with diabetic nephropathy possibly through inhibition of NF-κB signal pathway.
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2015年第12期1111-1114,共4页
Chinese Journal of Diabetes
