目的 探讨金合欢素对糖尿病肾病（DN）大鼠肾损伤及Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。方法 通过高脂高糖饲料喂养及ip链脲佐菌素（STZ）建立DN大鼠模型，将造模成功的大鼠随机分为模型组，金合欢素低、高剂量（40、80 mg ·kg-1）组，金合欢素（80 mg ·kg-1）＋脂多糖（LPS，0.1 mg ·kg-1）组，缬沙坦（20 mg ·kg-1）组，每组10只，并以正常喂养且不ip STZ的10只大鼠作为对照组。干预结束后，尾静脉取血，检测大鼠空腹血糖含量；收集大鼠24 h尿液，分析尿蛋白含量；腹部主动脉取血，ELISA法检测血清中血肌酐、血尿素氮水平及肿瘤坏死因子-α （TNF-α）、白细胞介素-6（IL-6）水平；分离双肾组织，透射电镜及HE染色检测肾组织损伤情况；Western blotting检测Toll样受体4（TLR4）/核因子-κB（NF-κB）通路相关蛋白表达。结果 与对照组比较，模型组肾组织严重受损，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著增加（P<0.05）；与模型组比较，缬沙坦和金合欢素低、高剂量组肾组织损伤得到缓解，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著降低（P<0.05）；与金合欢素高剂量组相比，金合欢素＋LPS组肾组织损伤加剧，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著增加（P<0.05）。结论 金合欢素通过抑制TLR4/NF-κB信号通路改善DN大鼠肾损伤。
Objective To investigate the effect of acacetin on renal injury and Toll like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in diabetes nephropathy (DN) rats. Methods The DN rat model was established by high fat and high sugar and ip injection of streptozotocin (STZ). The successful rats were randomly grouped into model group, acacetin low, high dose (40, 80 mg·kg-1) group, acacetin (80 mg·kg-1) + TLR4 activator LPS (0.1 mg ·kg-1) group, and valsartan (20 mg·kg-1) group, with 10 in each group, 10 normal fed rats were used as control group. After the intervention, blood was taken from the tail vein to detect the fasting blood glucose content of rats; urine of rats was collected for 24 hours, and urine protein content was analyzed; blood was taken from abdominal aorta, and the levels of serum creatinine, blood urea nitrogen and inflammatory factors - tumor necrosis factor (TNF- α), interleukin-6 (IL-6) were detected by ELISA; renal tissues were separated, the damage of renal tissue was detected by transmission electron microscopy and HE; and the expression of TLR4/NF-κB pathway related proteins was detected by Western blotting. Results Compared with the control group, the renal tissue in model group was severely damaged, the levels of blood glucose, urine protein, blood creatinine, blood urea nitrogen, TNF-α, IL-6, TLR4, and p-NF-κB p65/NF-κB p65 were significantly higher (P< 0.05). Compared with model group, the renal tissue damage in the acacetin low and high dose group was alleviated, the levels of blood glucose, urine protein, blood creatinine, blood urea nitrogen, TNF-α, IL-6, TLR4, p-NF-κB p65/NF-κB p65 were significantly lower (P< 0.05). Compared with the acacetin high dose group, the renal tissue damage in the acacetin high dose + LPS group was further aggravated, the levels of blood glucose, urine protein, blood creatinine, blood urea nitrogen, TNF-α, IL-6, TLR4, p-NF-κB p65/NF-κB p65 were significantly higher (P< 0.05), however, there was no significant difference in all indicators in the valsartan group. Conclusion Acacetin can ameliorate renal damage in DN rats by inhibiting TLR4/NF-κB signaling pathway.