目的 探討金合歡素對(duì)糖尿病腎病（DN）大鼠腎損傷及Toll樣受體4（TLR4）/核因子-κB（NF-κB）信號(hào)通路的影響。方法 通過高脂高糖飼料喂養(yǎng)及ip鏈脲佐菌素（STZ）建立DN大鼠模型，將造模成功的大鼠隨機(jī)分為模型組，金合歡素低、高劑量（40、80 mg ·kg^-1）組，金合歡素（80 mg ·kg^-1）＋脂多糖（LPS，0.1 mg ·kg^-1）組，纈沙坦（20 mg ·kg^-1）組，每組10只，并以正常喂養(yǎng)且不ip STZ的10只大鼠作為對(duì)照組。干預(yù)結(jié)束后，尾靜脈取血，檢測大鼠空腹血糖含量；收集大鼠24 h尿液，分析尿蛋白含量；腹部主動(dòng)脈取血，ELISA法檢測血清中血肌酐、血尿素氮水平及腫瘤壞死因子-α （TNF-α）、白細(xì)胞介素-6（IL-6）水平；分離雙腎組織，透射電鏡及HE染色檢測腎組織損傷情況；Western blotting檢測Toll樣受體4（TLR4）/核因子-κB（NF-κB）通路相關(guān)蛋白表達(dá)。結(jié)果 與對(duì)照組比較，模型組腎組織嚴(yán)重受損，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、腎組織TLR4和p-NF-κB p65/NF-κB p65蛋白表達(dá)顯著增加（P<0.05）；與模型組比較，纈沙坦和金合歡素低、高劑量組腎組織損傷得到緩解，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、腎組織TLR4和p-NF-κB p65/NF-κB p65蛋白表達(dá)顯著降低（P<0.05）；與金合歡素高劑量組相比，金合歡素＋LPS組腎組織損傷加劇，血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、腎組織TLR4和p-NF-κB p65/NF-κB p65蛋白表達(dá)顯著增加（P<0.05）。結(jié)論 金合歡素通過抑制TLR4/NF-κB信號(hào)通路改善DN大鼠腎損傷。

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.

R285.5

蘇州市科學(xué)技術(shù)局項(xiàng)目（SYSD2019070）