Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, No. 528 Zhangheng Road, Shanghai 201203, China.
Department of Internal Medicine, Shanghai TCM-Integrated Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, No. 184 Road Baoding, Shanghai 200082, China.
Biomed Pharmacother. 2021 Oct;142:111907. doi: 10.1016/j.biopha.2021.111907. Epub 2021 Jul 30.
Huangqi Guizhi Wuwu Decoction(HQGZWWD) is a Traditional Chinese Medicine formula from Synopsis of Golden Chamber used to treat blood arthralgia. According to the principle that the same treatment can be used for different diseases, HQGZWWD has proven effective for IgA nephropathy (IgAN) associated with spleen and kidney yang deficiency.
In this study, we investigated the mechanism by which HQGZWWD alleviates proteinuria and protects renal function in rats with IgAN by regulating the AT1R/Nephrin/c-Abl pathway.
Rats were randomly divided into six groups: control, IgAN model, IgAN model treated with low-dose HQGZWWD, IgAN model treated with medium-dose HQGZWWD, IgAN model treated with high-dose HQGZWWD, and IgAN model treated with valsartan. IgAN was induced using bovine γ-globulin. We evaluated the mediating effects of HQGZWWD on podocyte cytoskeletal proteins, the AT1R/Nephrin/c-Abl pathway, upstream tumor necrosis factor-α (TNF-α), and TNF-α receptor-1 (TNFR1).
The IgAN rats displayed proteinuria, IgA deposition in the mesangial region, and podocyte cytoskeletal protein damage. The expression of TNF-α, TNFR1, AT1R, and c-Abl was increased in the IgAN rat kidney, whereas the expression of nephrin, podocin, ACTN4, and phosphorylated nephrin (p-nephrin) was reduced. HQGZWWD treatment significantly alleviated podocyte cytoskeletal protein damage in the IgAN rats, upregulated the expression of nephrin, podocin, and ACTN4, and the colocalized expression of F-actin and nephrin. This study demonstrates that HQGZWWD attenuates podocyte cytoskeletal protein damage by regulating the AT1R-nephrin- c-Abl pathway, upregulating the expression of p-nephrin, and downregulating the expression of AT1R and c-Abl.
These results indicate that HQGZWWD attenuates podocyte cytoskeletal protein damage in IgAN rats by regulating the AT1R/Nephrin/c-Abl pathway, providing a potential therapeutic approach for IgAN.
黄芪桂枝五物汤（HQGZWWD）是《金匮要略》中的一种中药方剂，用于治疗血痹。根据同病异治的原则，HQGZWWD 已被证明对脾肾阳虚型 IgA 肾病（IgAN）有效。
本研究通过调节 AT1R/Nephrin/c-Abl 通路，探讨 HQGZWWD 减轻 IgA 肾病大鼠蛋白尿、保护肾功能的作用机制。
大鼠随机分为六组：对照组、IgAN 模型组、HQGZWWD 低剂量组、HQGZWWD 中剂量组、HQGZWWD 高剂量组和缬沙坦组。采用牛γ球蛋白诱导 IgAN。评价 HQGZWWD 对足细胞骨架蛋白、AT1R/Nephrin/c-Abl 通路、上游肿瘤坏死因子-α（TNF-α）和 TNF-α 受体-1（TNFR1）的调节作用。
IgAN 大鼠出现蛋白尿、系膜区 IgA 沉积和足细胞骨架蛋白损伤。IgAN 大鼠肾脏 TNF-α、TNFR1、AT1R 和 c-Abl 表达增加，而 Nephrin、podocin、ACTN4 和磷酸化 Nephrin（p-Nephrin）表达减少。HQGZWWD 治疗可明显减轻 IgAN 大鼠足细胞骨架蛋白损伤，上调 Nephrin、podocin 和 ACTN4 的表达，以及 F-肌动蛋白和 Nephrin 的共定位表达。本研究表明，HQGZWWD 通过调节 AT1R-Nephrin-c-Abl 通路，上调 p-Nephrin 的表达，下调 AT1R 和 c-Abl 的表达，减轻足细胞骨架蛋白损伤。
这些结果表明，HQGZWWD 通过调节 AT1R/Nephrin/c-Abl 通路减轻 IgAN 大鼠足细胞骨架蛋白损伤，为 IgAN 的治疗提供了一种潜在的方法。
