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乙型肝炎病毒(HBV)感染导致肝损伤时 RNA 的氧化损伤增加。

Increased oxidative damage of RNA in liver injury caused by hepatitis B virus (HBV) infection.

机构信息

a Department of Clinical Laboratory , Beijing Ditan Hospital, Capital Medical University , Beijing , China.

b National Center of Gerontology, MOH Key Laboratory of Geriatrics, Beijing Hospital , Beijing , China.

出版信息

Free Radic Res. 2018 Apr;52(4):426-433. doi: 10.1080/10715762.2018.1439165. Epub 2018 Feb 27.

Abstract

To evaluate the urinary levels of 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in liver injury patients with hepatitis B virus (HBV) infection and to explore the relationship between urinary 8-oxo-dGsn or 8-oxo-Gsn and degree of liver damage. We enrolled 138 liver injury patients with HBV infection and 169 age- and sex-matched healthy controls in this study. A sensitive and accurate isotope-diluted liquid chromatograph mass spectrometer/mass spectrometer (LC-MS/MS) method was used to measure the urinary levels of 8-oxo-Gsn and 8-oxo-dGsn. Simultaneously, pathological analysis of liver biopsy tissues was carried out, and immunohistochemistry was carried out for 8-oxo-Guo, 8-oxo-dGuo and MTH1 protein in some liver injury tissues. We analysed the correlation between the degrees of inflammation and fibrosis and levels of 8-oxo-Gsn and 8-oxo-dGsn. We also analysed the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn with clinical data of HBeAg, HBsAg, and HBV genotype and detected the levels of plasma aspartate aminotransferase, alanine aminotransferase (AST), platelet, alkaline phosphatase, prothrombin time (PT) and HBV DNA, and calculated the aspartate amino transferase-to-platelet ratio index (APRI) score. Nonparametric correlations were used to evaluate the correlation between 8-oxo-Gsn, 8-oxo-dGsn or APRI and various laboratory biochemical indicators. Results showed that the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn in patients with liver injury were significantly higher than those of healthy controls (both p < .001). Urinary 8-oxo-Gsn was significantly associated with AST, APRI and PT (p = .013, p = .026 and p = .049). The receiver operating characteristic curves of 8-oxo-Gsn were 0.696 (0.632-0.759) and 0.731 (0.672-0.790) for inflammatory activity and fibrosis, respectively. Patients with higher levels of urinary 8-oxo-Gsn are more likely to have a high degree of fibrosis and urinary 8-oxo-Gsn may have a great potential in assessing liver fibrosis.

摘要

目的

评估乙型肝炎病毒(HBV)感染所致肝损伤患者尿 8-氧-7,8-二氢-2'-脱氧鸟苷(8-oxo-dGsn)和 8-氧-7,8-二氢鸟苷(8-oxo-Gsn)的水平,并探讨尿 8-氧-dGsn 或 8-氧-Gsn 与肝损伤程度的关系。

方法

本研究纳入了 138 例 HBV 感染所致肝损伤患者和 169 名年龄和性别匹配的健康对照者。采用灵敏、准确的同位素稀释液相色谱-质谱联用(LC-MS/MS)法测定尿 8-氧-Gsn 和 8-氧-dGsn 的水平。同时对肝活检组织进行病理分析,并对部分肝损伤组织中的 8-氧-Guo、8-氧-dGuo 和 MTH1 蛋白进行免疫组化染色。分析炎症和纤维化程度与 8-氧-Gsn 和 8-氧-dGsn 水平之间的相关性。分析尿 8-氧-Gsn 和 8-氧-dGsn 与 HBeAg、HBsAg、HBV 基因型等临床数据的关系,并检测血浆天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血小板、碱性磷酸酶、凝血酶原时间(PT)和 HBV DNA 水平,计算天冬氨酸氨基转移酶/血小板比值指数(APRI)评分。采用非参数相关性分析评估 8-氧-Gsn、8-氧-dGsn 或 APRI 与各种实验室生化指标的相关性。

结果

肝损伤患者尿 8-氧-Gsn 和 8-氧-dGsn 水平明显高于健康对照组(均 P<0.001)。尿 8-氧-Gsn 与 AST、APRI 和 PT 显著相关(P=0.013、P=0.026 和 P=0.049)。8-氧-Gsn 的受试者工作特征曲线(ROC)下面积分别为 0.696(0.632-0.759)和 0.731(0.672-0.790),用于评估炎症活动度和纤维化程度。尿 8-氧-Gsn 水平较高的患者更容易出现严重纤维化,尿 8-氧-Gsn 可能具有很大的评估肝纤维化的潜力。

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