Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Jichang Road, Guangzhou, 510000, China.
Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China.
J Pharm Pharmacol. 2024 Sep 3;76(9):1149-1159. doi: 10.1093/jpp/rgae095.
Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection.
Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study.
The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions.
These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.
糖尿病肾病(DN)是导致终末期肾衰竭的主要原因,目前缺乏有效的治疗方法。圣青降脂胶囊(SQJZJN)是一种治疗慢性肾病的中药方剂,其在保护肾脏方面的作用尚未得到充分研究。
本研究采用 8 周龄雄性 C57BLKS/J db/db、C57BLKS/J db/m 小鼠和高糖培养的人肾小球系膜细胞(HMC)作为实验模型。
体内研究表明,SQJZJN 可显著改善 db/db 小鼠的肾脏病理损伤,降低血清肌酐和尿微量白蛋白水平。体外实验表明,SQJZJN 可减轻晚期糖基化终产物(AGEs)和活性氧(ROS)的产生,减少肾脏细胞凋亡。机制上,SQJZJN 通过促进核因子红细胞衍生 2 相关因子 2(Nrf2)、γ-谷氨酰半胱氨酸合成酶重链(γ-GCS)和血红素加氧酶-1(HO-1)的表达,同时降低 Kelch 样 ECH 相关蛋白 1(KEAP1)的表达,激活 Keap1/Nrf2/ARE 通路。
这些发现表明,SQJZJN 对 DN 具有保护作用,可能通过激活 Keap1/Nrf2/ARE 通路。