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NOX2产生的氧化应激与非酒精性脂肪性肝病患者肝脏超声脂肪变性的严重程度相关。

NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease.

作者信息

Del Ben Maria, Polimeni Licia, Carnevale Roberto, Bartimoccia Simona, Nocella Cristina, Baratta Francesco, Loffredo Lorenzo, Pignatelli Pasquale, Violi Francesco, Angelico Francesco

机构信息

Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy.

出版信息

BMC Gastroenterol. 2014 Apr 23;14:81. doi: 10.1186/1471-230X-14-81.

Abstract

BACKGROUND

Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.

METHODS

The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels.

RESULTS

Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed.

CONCLUSIONS

We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver steatosis at ultrasound.

摘要

背景

慢性氧化应激是非酒精性脂肪性肝病疾病进展的关键机制之一。然而,迄今为止,很少有研究报道非酒精性脂肪肝患者循环氧化应激标志物水平升高,并且尚未使用全身氧化应激的新标志物进行研究。目的是评估非酒精性脂肪肝患者尿8-异前列腺素F2α和血清可溶性NOX2衍生肽与肝脂肪变性严重程度之间的关系。

方法

该研究对264例因疑似代谢疾病转诊的连续患者进行。根据滨口超声标准定义脂肪变性。通过尿8-异前列腺素F2α和血清可溶性NOX2衍生肽水平评估氧化应激。

结果

与无脂肪肝的患者相比,非酒精性脂肪肝患者的尿8-异前列腺素F2α、血清可溶性NOX2衍生肽、丙氨酸转氨酶、细胞角蛋白-18和胰岛素抵抗稳态模型的平均值更高(p<0.001),血清脂联素值更低。非酒精性脂肪肝患者代谢综合征及其临床特征的患病率显著更高。在排除肥胖受试者、糖尿病或代谢综合征患者以及未服用他汀类药物的患者后,也观察到了相同的结果。此外,尿8-异前列腺素F2α水平是非酒精性脂肪肝的独立预测因子,并且还观察到尿8-异前列腺素F2α和血清可溶性NOX2衍生肽与超声检查时脂肪变性严重程度之间存在强关联。

结论

我们证明了非酒精性脂肪肝患者氧化应激标志物升高。尿8-异前列腺素F2α和血清可溶性NOX2衍生肽水平独立于肥胖、糖尿病和代谢综合征,并随着超声检查时肝脂肪变性严重程度的增加而升高。

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