School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan.
PLoS One. 2020 Oct 26;15(10):e0241053. doi: 10.1371/journal.pone.0241053. eCollection 2020.
The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.
研究了在加速性抗肾小球基底膜肾炎(NTS)肾炎的小鼠中,甲基乙二醛(MGO)与 D-乳酸盐(D-lactate)之间的关系。通过给予 C57BL/6 小鼠抗基底膜抗体来诱导 NTS 肾炎,并给予三种剂量的柴胡皂苷 C(SSC)治疗 14 天。检测蛋白尿、血尿素氮、血清肌酐、肾组织学、尿 MGO 和 D-乳酸盐的变化。与 NTS 对照组相比,中剂量(10mg/kg/天)的 SSC 基于尿蛋白测量明显减轻了肾炎的发展(34.40±6.85 vs. 17.33±4.79mg/天,p<0.05)。肾小球基底膜(GBM)的病理观察显示单核细胞浸润、肥大和新月体得到缓解,损伤评分也显示中剂量 SSC 在肾炎期间的疗效改善(7.92±1.37 vs. 3.50±1.14,p<0.05)。此外,尿 MGO 水平的显著降低(24.71±3.46 vs. 16.72±2.36μg/mg,p<0.05)和 D-乳酸盐(0.31±0.04 vs. 0.23±0.02μmol/mg,p<0.05)与生化和病理检查一致。本研究表明,MGO 和 D-乳酸盐可能反映了 NTS 肾炎的损伤程度和 SSC 的疗效;需要进一步的研究才能实现临床应用。