Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway.
Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway.
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三七口服液通过 Nrf2/HO-1 通路减轻大鼠被动海曼肾炎蛋白尿并阻断足细胞凋亡
DOI：
10.3389/fphar.2021.727874
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发表时间：
2021
影响因子：
5.6
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Wang X;Liu J;Tian R;Zheng B;Li C;Huang L;Lu Z;Zhang J;Mao W;Liu B;Bao K;Xu P
特发性膜性肾病（IMN）是成人肾病综合征中最常见的病理类型，足细胞凋亡被发现介导蛋白尿的发生。三七口服液（SQ）是临床上用于治疗IMN数十年的有效中药制剂，在降低蛋白尿方面发挥着重要作用，但其潜在机制尚未完全阐明。目前的研究验证了 SQ 通过减少足细胞凋亡直接减少 IMN 蛋白尿的假设。为了研究SQ的作用，我们建立了体内抗Fx1A抗血清诱导的实验性被动海曼肾炎（PHN）大鼠模型和体外盐酸阿霉素（ADR）损伤足细胞凋亡模型。 SQ干预显着降低了PHN大鼠的蛋白尿水平，同时降低了大鼠抗兔IgG抗体、补体C3和C5b-9在肾小球中的沉积，并伴有血清白蛋白升高。足细胞损伤标志物突触足蛋白的表达在 SQ 给药后恢复，而电镜分析表明足突融合和肾小球基底膜粗突明显减弱。进一步研究表明，SQ治疗可显着抑制PHN大鼠和ADR损伤足细胞的足细胞凋亡，体内外Cleaved Caspase-3蛋白水平或Bax/Bcl-2比值均显着降低。此外，我们发现核因子红细胞2相关因子2/血红素加氧酶1（Nrf2/HO-1）途径介导SQ在足细胞中的抗凋亡作用。因此，SQ 通过 Nrf2/HO-1 途径减轻 PHN 大鼠的足细胞凋亡和蛋白尿。
Idiopathic membranous nephropathy (IMN) is the most common pathological type in adult nephrotic syndrome where podocyte apoptosis was found to mediate the development of proteinuria. Sanqi oral solution (SQ), an effective Chinese herbal preparation clinically used in treatment of IMN for decades, plays an important role in reducing proteinuria, but the underlying mechanisms have not been fully elucidated yet. The current study tested the hypothesis that SQ directly lessens proteinuria in IMN by reducing podocyte apoptosis. To investigate the effects of SQ, we established the experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum in vivo and doxorubicin hydrochloride (ADR)-injured apoptotic podocyte model in vitro. SQ intervention dramatically reduced the level of proteinuria, together with the rat anti-rabbit IgG antibodies, complement C3, and C5b-9 deposition in glomerulus of PHN rats, accompanied by an elevation of serum albumin. Protein expression of synaptopodin, marker of podocyte injury, restored after SQ administration, whereas the electron microscopic analysis indicated that fusion of foot processes, and the pachynsis of glomerular basement membrane was markedly diminished. Further studies showed that SQ treatment could significantly inhibit podocyte apoptosis in PHN rats and ADR-injured podocytes, and protein levels of Cleaved Caspase-3 or the ratio of Bax/Bcl-2 were significantly decreased with SQ treatment in vivo or in vitro. Moreover, we found that the nuclear factor erythroid 2–related factor-2/heme oxygenase 1 (Nrf2/HO-1) pathway mediated the anti-apoptosis effective of SQ in podocyte. Thus, SQ mitigates podocyte apoptosis and proteinuria in PHN rats via the Nrf2/HO-1 pathway.
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