儿童原发性EB病毒感染caspase-3／6水平与肝损害的相关性研究

Correlation between caspase-3/6 levels and EBV-induced liver injury in children

目的研究不同发病时期和年龄儿童原发性EB病毒（Epstein—Barrvirus，EBV）感染肝功能损害与含半胱氨酸的天冬氨酸蛋白水解酶3（caspase-3）及含半胱氨酸的天冬氨酸蛋白水解酶6（caspase-6）的相关性。方法收集2016年7月至2017年6月在温州医科大学附属第二医院住院确诊为原发性EBV感染患儿249例，1到14岁。168例有肝功能损伤的患儿为肝功能异常组，检测急性期和恢复期指标，剩余81例为肝功能正常组。肝功能异常组再分4个亚组：幼儿组37例，学龄前组50例，学龄组36例，青少年组45例。检测谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBLL）、谷氨酰转移酶（GGT）和直接胆红素（DBLL），ELISA法检测caspase-3／6的分子蛋白含量。结果肝功能异常组相较于肝功能正常组caspase3／6升高，差异具有统计学意义（P均〈0．001）；急性期caspase3／6相较于恢复期升高，差异有统计学意义（P均〈0．001）；青少年组ALT、caspase-3／6相较于其他3组差异具有统计学意义（P均〈0．001），余各组之间差异无统计学意义；AST、TBLL、GGT和DBLL比较差异均无统计学意义；急性期ALT与caspase-3／6之间存在线性相关（r=0．982，r=0．965，P均〈0．001），恢复期则无相关性。结论EBV感染导致肝功能损伤的过程中，急性期caspase-3／6和ALT之间的升高存在线性相关，提示EBV导致的肝功能损伤与caspase-3／6密切相关。

Objective To investigate the relationship between the EBV-induced liver injury and caspase-3/6 in children. Methods Data of 249 patients seen from July 2016 to June 2017 who got infection with EBV were collected in second affiliated hospital of Wenzhou Medical University anti the patients were divided into two groups; 168 patients who were diagnosed with hepatitis were selected for abnormal liver function group,laboratory tests were performed in acute phase and convalescent phase. Meanwhile the 81 patients,whose liver function were normal were selected for normal liver function group. Two ml of blood plasma was collected from each patient from both groups at the beginning and after a week＇ s treatment of the abnormal liver function group. The patients were aged from 1 to 14 years. The abnormal liver function group was further divided into four groups： young children （ 1-3 years old） , preschool children （4-6 years old） , school children （7-10 years old）, teenagers （10-14 years old）. Firstly, we recorded their alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBIL）, gamma glutamyl transpeptidase （GGT） and direct bilirubin （DBIL） , then by the use of enzyme linked immunosorbent assay （ELISA） we measured the protein level of caspase-3 and caspase-6. Results In the group of abnormal liver function group, in the acute phase of the teenagers the level of ALT, caspase-3 and caspase-6 are improved significantly（ 927.2±82.5 vs. 158.5±41.4, P〈0.001,169.8 ±52.8 vs. 91.5 ±10.1, P〈0.001,P〈 0.05,82.2± 2.6, P 〈0.001,965.8 ±31.5, P 〈0.001,184.8 ± 14.3, P 〈 0.001）,while the AST, TBLL, GGT and DBLL had no significant difference. Conclusions In the process of EBV-induced liver injury, there was a linear correlation between the increase of caspase-3/6 and ALT in the acute stage, suggesting that EBV-induced liver injury is closely related to caspase-3/6.