Division of Nephropathy, Department of Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Nephrology (Carlton). 2013 Oct;18(10):690-9. doi: 10.1111/nep.12128.
Oxidative stress plays an important role in the progression of renal interstitial fibrosis. The nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (Nox) family is considered one of the major sources of reactive oxygen species (ROS). In the present study, we investigated the inhibitory effects of a novel anti-fibrotic agent, Fluorofenidone (AKF-PD), upon Nox-mediated oxidative stress and deposition of extracellular matrix (ECM) in the development of renalinterstitial fibrosis.
AKF-PD was used to treat renal fibrosis in unilateral ureteral obstruction (UUO) obstructive nephropathy in rats. The expression of Nox homologues, p-Akt, collagen I and III were detected by immunoblotting or immunohistochemistry. Levels of 8-iso prostaglandin F2alpha (8-Iso PGF2a) was measured by enzyme linked immunosorbent assay. In addition, ROS and the expression of collagen I (1a), Nox subunits and p-Akt was measured in angiotensin (Ang) II-stimulated rat proximal tubular epithelial (NRK-52E) cells in culture.
AKF-PD treatment significantly attenuated tubulo-interstitial injury, ECM deposition and oxidative stress in fibrotic rat kidneys. In addition, AKF-PD inhibited the expression of ROS, Collagen I (1a), Nox2, p-Akt in Ang II-stimulated NRK-52E cells.
AKF-PD attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and ECM deposition via the PI3K/Akt signalling pathway, suggesting AKF-PD is a potential novel therapeutic agent against renal fibrosis.
氧化应激在肾间质纤维化的进展中起着重要作用。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（Nox）家族被认为是活性氧（ROS）的主要来源之一。在本研究中，我们研究了新型抗纤维化剂氟洛芬定（AKF-PD）对 Nox 介导的氧化应激和细胞外基质（ECM）沉积在肾间质纤维化发展中的抑制作用。
AKF-PD 用于单侧输尿管梗阻（UUO）梗阻性肾病大鼠肾纤维化的治疗。通过免疫印迹或免疫组化检测 Nox 同源物、p-Akt、胶原 I 和 III 的表达。通过酶联免疫吸附试验测量 8-异前列腺素 F2alpha（8-Iso PGF2a）的水平。此外，还测量了在血管紧张素（Ang）II 刺激的大鼠近端肾小管上皮（NRK-52E）细胞培养物中 ROS 的表达和胶原 I（1a）、Nox 亚基和 p-Akt 的表达。
AKF-PD 治疗显著减轻了纤维化大鼠肾脏的肾小管间质损伤、ECM 沉积和氧化应激。此外，AKF-PD 抑制了 Ang II 刺激的 NRK-52E 细胞中 ROS、胶原 I（1a）、Nox2、p-Akt 的表达。
AKF-PD 通过抑制 PI3K/Akt 信号通路抑制 NADPH 氧化酶和 ECM 沉积，部分减轻了肾间质纤维化的进展，这表明 AKF-PD 是一种潜在的新型肾纤维化治疗药物。
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