【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、糖尿病肾病模型（M）组及TAK-242治疗（TAK-242）组。腹腔一次性注射STZ（60 mg/kg）建立糖尿病肾病大鼠模型。造模成功后4、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(IKBα)、p65、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可减轻糖尿病肾病大鼠肾脏组织中核内p65含量，以及TNF-α和MCP-1的表达，抑制IkBα的降解（P<0.05）。 结论    TAK-242对糖尿病肾病大鼠有保护作用，其机制可能与抑制NF-kB信号通路相关。

      【关键词】 糖尿病肾病；TAK-242；大鼠

    Protective effect of toll-like receptor 4 inhibitor TAK-242 on kidney in rats with diabetic nephropathy 

   【Abstract】  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 4 and 8 weeks after modeling. Protein expression levels of human nuclear factor κb inhibitor protein α (IκBα), p65, TNF-α and monocyte chemoattrac-tant 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 p65 and expression levels of TNF-α and MCP-1 were significantly lower while IκBα level 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.

      【Key words】  Diabetic nephropathy; TAK-242; Rat