研究动态
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载脂蛋白A-I通过抑制氧化应激和炎症作用,减轻腹腔透析相关的腹膜纤维化。

Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation.

发表日期:2023
作者: Jing Lu, Jie Gao, Jing Sun, Haiping Wang, Huijuan Sun, Qian Huang, Yao Zhang, Shuo Zhong
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

载脂蛋白A-I (apoA-I) 是高密度脂蛋白 (HDL) 中的主要成分,其中90%存在,具有抗炎和抗氧化性质,在抗动脉粥样硬化方面受到了广泛关注。然而,有关apoA-I在腹膜透析中的作用知之甚少。本研究通过分析81例PD患者,发现apoA/HDL-C比值降低与腹膜功能迅速下降显著相关。进一步的动物实验研究确定了载脂蛋白A-I类似肽(D-4F)对腹膜的优越性,我们发现D-4F的给予减少了高葡萄糖腹膜透析液引起的腹膜纤维化和腹膜内皮间质转化(EMT),例如N-钙黏蛋白、纤连蛋白、波形蛋白和α-平滑肌肌动蛋白 (α-SMA)的表达降低。在机制方面,D-4F可以显著抑制Smad2/3磷酸化,这是导致纤维化的主要通路。此外,D-4F治疗抑制了NADPH氧化酶和硫代巴比妥酸反应物 (TBARS)的表达,增加了一些酶的活性,例如超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-Px)。最后,D-4F治疗抑制了白细胞介素-6 (IL-6)、白细胞介素-1β (IL-1β) 和肿瘤坏死因子-α (TNF-α) 的表达。综上所述,基于上述研究证据,apoA-I及其肽类模拟物可能通过调节氧化应激、TGF-β1/Smads信号通路和炎症反应来减少腹膜透析引起的腹膜纤维化。Copyright © 2023 Lu, Gao, Sun, Wang, Sun, Huang, Zhang and Zhong.
Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I 's role in peritoneal dialysis. In this study, by analyzing PD patients (n = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis.Copyright © 2023 Lu, Gao, Sun, Wang, Sun, Huang, Zhang and Zhong.