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[急性胰腺炎患者循环中miR-29a上调,且与疾病严重程度及不良预后呈正相关]

[Up-regulation of circulating miR-29a in patients with acute pancreatitis and is positively correlated with disease severity and poor prognosis].

作者信息

Gao Ming, Bian Erbao, Li He, Ge Weiwei, Yin Chunlin, Wang Haiping, Sun Yuansong

机构信息

Department of Emergency Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China. *Corresponding author, E-mail:

Central Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018 Oct;34(10):931-936.

PMID:30554587
Abstract

Objective To investigate the clinical application value of circulating miR-29a in diagnosis and prognosis monitoring in acute pancreatitis (AP) patients, and to preliminary explore the molecular pathology significance of high expression of miR-29a. Methods 30 cases of mild acute pancreatitis (MAP) patients (MAP group) and 30 cases of moderately serve acute pancreatitis (MSAP) or serve acute pancreatitis (SAP) patients ( M-SAP group) were randomly selected, and 30 cases of healthy adults were used as control group. The general clinical data of each group were compared, and miR-29a levels in peripheral blood were measured by real tome quantitative PCR, then the correlation between miR-29a levels and Ranson score or APACHEIIscore were analyzed. The clinical usefulness of miR-29a for AP patients was assessed by ROC curve analysis. AR42J cells were treated with deoxycholic acid (DCA) to establish AP cell model, the expression levels of miR-29a and caspase-3 were detected. AR42J cells were transfected by lentiviral vector contain miR-29a mimic or miR-29a AMO and measured of expression levels of miR-29a and caspase-3. Results In acute phase, the expression of circulating miR-20a was up-regulated in MAP and M-SAP group patients, and miR-20a levels of M-SAP group patients were higher than MAP group patients. In same group, miR-20a levels in acute phase were higher than recovery phase. Correlation analysis indicated the positive correlation between miR-20a levels and Ranson score or APACHEII score. ROC curve analysis indicated that the AUC of miR-29a for diagnosis MAP patients was 0.961 ( 95%CI: 0.921~ 1.002), cut-off value was 1.460. The AUC of miR-29a for diagnosis M-SAP patients was 0.972 ( 95%CI: 0.939 ~ 1.004), cut-off value was 1.340. The expression levels of miR-29a and caspase 3 were increased in AP cell model. Moreover, caspase 3 levels in AP cell model were increased than vector control after overexpression of miR-29a, and caspase-3 levels were reduced than vector control after suppressing of miR-29a expression. Conclusion Circulating miR-29a is high expression in MAP and M-SAP patients, and high expression of miR-29a may relate to pancreatic acinar cell apoptosis, and this biomarkers has high clinical value in AP diagnosis and prognosis monitoring.

摘要

目的 探讨循环miR-29a在急性胰腺炎(AP)患者诊断及预后监测中的临床应用价值,并初步探讨miR-29a高表达的分子病理学意义。方法 随机选取30例轻症急性胰腺炎(MAP)患者(MAP组)和30例中度重症急性胰腺炎(MSAP)或重症急性胰腺炎(SAP)患者(M-SAP组),另选取30例健康成年人作为对照组。比较各组一般临床资料,采用实时定量PCR检测外周血miR-29a水平,分析miR-29a水平与Ranson评分或APACHEII评分的相关性。通过ROC曲线分析评估miR-29a对AP患者的临床诊断价值。用脱氧胆酸(DCA)处理AR42J细胞建立AP细胞模型,检测miR-29a和caspase-3的表达水平。用含miR-29a模拟物或miR-29a反义寡核苷酸的慢病毒载体转染AR42J细胞,检测miR-29a和caspase-3的表达水平。结果 急性期,MAP组和M-SAP组患者循环miR-29a表达上调,且M-SAP组患者miR-29a水平高于MAP组患者。同组内,急性期miR-29a水平高于恢复期。相关性分析表明miR-29a水平与Ranson评分或APACHEII评分呈正相关。ROC曲线分析显示,miR-29a诊断MAP患者的AUC为0.961(95%CI:0.9211.002),截断值为1.460。miR-29a诊断M-SAP患者的AUC为0.972(95%CI:0.9391.004),截断值为1.340。AP细胞模型中miR-29a和caspase 3表达水平升高。此外,miR-29a过表达后,AP细胞模型中caspase 3水平高于载体对照组,miR-29a表达受抑制后,caspase-3水平低于载体对照组。结论 循环miR-29a在MAP和M-SAP患者中高表达,miR-29a高表达可能与胰腺腺泡细胞凋亡有关,该生物标志物在AP诊断及预后监测中具有较高临床价值。

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