Does Nox2 Overactivate in Children with Nonalcoholic Fatty Liver Disease?
Does Nox2 Overactivate in Children with Nonalcoholic Fatty Liver Disease?
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DOI：
10.1089/ars.2018.7596
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发表时间：
2019-04-01
影响因子：
6.6
通讯作者：
Nobili, Valerio
中科院分区：
文献类型：
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作者：
Loffredo, Lorenzo;Zicari, Anna Maria;Nobili, Valerio
目前尚不清楚烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2 （Nox2）激活是否与非酒精性脂肪性肝病（NAFLD）的内毒素血症和肝损伤早期相关。为了解决这个问题，我们评估了67名活检证实的NAFLD儿童和73名对照组的Nox2激活、氧化应激、肠道通透性和脂多糖（LPS）血清水平。与对照组相比，NAFLD患者具有更高的Nox2活性、异前列腺素、zonulin和LPS水平。多元线性回归分析显示，甘油三酯、高密度脂蛋白（HDL）、稳态模型评估-估计胰岛素抵抗（HOMA-IR）、脂多糖（LPS）和异前列腺素与nox2衍生物肽（sNox2-dp）水平独立相关。在NAFLD组中，非酒精性脂肪性肝炎（NASH）患者的sNox2-dp、异前列腺素、LPS、甘油三酯、HOMA-IR、空腹血糖和胰岛素水平显著高于非NASH患者，HDL水平显著低于非NASH患者。此外，sNox2-dp水平与脂肪变性、炎症、气球化、纤维化和NAFLD活动评分的组织学分级呈线性相关。本研究提供的证据表明，与对照组相比，NAFLD儿童存在Nox2过度激活，且与肝损害程度显著相关。Nox2和LPS血清水平之间的密切关系使我们假设肠道源性LPS在诱导全身Nox2激活中可能起作用。
It is unknown whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2) activation is early associated with endotoxemia and liver damage in nonalcoholic fatty liver disease (NAFLD). To address this issue, we evaluated Nox2 activation, oxidative stress, gut permeability, and lipopolysaccharide (LPS) serum levels in 67 children with biopsy-proven NAFLD and 73 controls. Compared with controls, NAFLD patients had higher Nox2 activity, isoprostane, zonulin, and LPS levels. Multivariate linear regression analysis showed that triglycerides, high-density lipoprotein (HDL), homeostatic model assessment-estimated insulin resistance (HOMA-IR), LPS, and isoprostanes were independently associated with Nox2-derivative peptide (sNox2-dp) levels. Within the NAFLD group, patients with nonalcoholic steatohepatitis (NASH) had significant higher levels of sNox2-dp, isoprostanes, LPS, triglycerides, HOMA-IR, fasting glucose and insulin, and lower HDL than those without NASH. Furthermore, sNox2-dp levels were linearly associated with the histological grading of steatosis, inflammation, ballooning, fibrosis, and NAFLD activity score. This study provides evidence that children with NAFLD have Nox2 overactivation compared with controls and significant association with the degree of liver damage. The close relationship between Nox2 and LPS serum levels leads to hypothesize a potential role for gut-derived LPS in eliciting systemic Nox2 activation.