Ma Shi-Xing, Li Xiao-Jun, Duan Ting-Ting, Pei Ming, Zou Liang, Yu Xiao-Yong, Zhao Ying-Yong
Department of Nephrology, Baoji Central Hospital, Baoji, Shaanxi 721008, China.
Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510315, China.
Heliyon. 2023 Sep 9;9(9):e20019. doi: 10.1016/j.heliyon.2023.e20019. eCollection 2023 Sep.
Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal and its four downstream target genes including , , and compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of -IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47 and p67, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.
在阐明特发性膜性肾病(IMN)患者潜在的病理机制方面取得了相当大的成就。尽管IMN患者在肾衰竭之前就能得到很好的诊断,但目前尚无有效的药物干预措施能阻止IMN的进展。在本研究中,我们评估了摩肾颗粒(MSG)对IMN患者和阳离子牛血清白蛋白(CBSA)诱导的大鼠的影响。越来越多的研究表明,芳烃受体(AHR)的激活与氧化应激和炎症有关。我们进一步确定了MSG对CBSA诱导的大鼠中AHR、核因子κB(NF-κB)和核因子红细胞2相关因子2(Nrf2)的影响。MSG显著降低了IMN患者和CBSA诱导的大鼠的蛋白尿并改善了肾功能。与未处理的CBSA诱导的大鼠相比,MSG显著抑制了肾内及其四个下游靶基因(包括 、 、 和 )mRNA表达的增加。这伴随着-IκBα和NF-κB p65及其下游基因产物(包括MCP-1、COX-2、12-LOX、iNOS、p47和p67)的蛋白表达显著下调,而肾组织中Nrf2及其下游基因产物(包括过氧化氢酶、HO-1、GCLM、GCLC、MnSOD和NQO1)的蛋白表达则显著保留。这些数据表明,MSG通过AHR信号通路抑制NF-κB/Nrf2途径的激活,从而减轻足细胞损伤。这一发现可能为通过氧化应激和炎症治疗IMN提供一种有前景的疗法。