microRNA在急性胰腺炎患者外周血中表达的意义

Significance of the expression of microRNA in the peripheral blood of patients with acute pancreatitis

目的 通过检测血清microRNA变化,预判急性胰腺炎的病情严重度并探讨影响经皮置管引流（PCD）治疗的因素.方法 回顾性分析2013年10月至2014年3月成都军区总医院收治的120例急性胰腺炎患者的临床资料并采集其外周血,35例急性重度胰腺炎（SAP）、急性中重度胰腺炎（MSAP）为A组,85例急性轻度胰腺炎（MAP）为B组.对所有患者进行APACHE Ⅱ、Reason、BISAP评分,用实时定量PCR法进行定量检测患者血清中miR-146a、miR-10b、miR-21、miR-26a表达水平,比较两组之间的4种microRNA表达差异以及与评分系统间的相关性,并分析影响PCD治疗的因素.计量资料采用t检验,变量间关系采用直线相关分析.单因素和多因素分析采用Logistic回归.结果 （1）APACHEⅡ、RANSON、BISAP评分：A组分别为（8.28±0.61）分、（3.42±0.54）分、（1.71±0.32）分;B组分别为（3.18±0.52）分、（1.43±0.25）分、（0.37±0.06）分,两组比较,差异有统计学意义（t=4.266,7.809,4.113,P＜0.05）.（2）血清miR-146a、miR-10b、miR-21、miR-26a表达水平：A组分别为1.41±0.21、2.94±0.49、1.62±0.25、1.21±0.20;B组分别为6.29±0.91、0.52±0.09、2.82±0.33、3.57±0.64.miR-146a、miR-10b在两组间差异有统计学意义（=-2.156,2.110,P＜0.05）,而miR-21、miR-26a两组间差异无统计学意义（t=-1.114,-1.571,P ＞0.05）.（3）相关性：A组miR-146a、miR-10b与APACHEⅡ、RANSON、BISAP评分有相关性（r=-0.826、0.837,-0.874、0.866,-0.833、0.899,P＜0.05）.而miR-21、miR-26a表达水平与APACHE Ⅱ、RANSON、BISAP评分无相关性（r=0.642、0.321,0.701、0.750,0.716、0.716,P＞0.05）.B组miR-146a、miR-10b、miR-21、miR-26a表达水平与APACHE Ⅱ评分无相关性（r=0.067,0.347,0.133,0.111,P＞0.05）;与RANSON评分无相关性（r =0.178,0.078,0.092,0.142,P＞0.05）;与BISAP评分无相关性（r=0.103,0.260,0.216,0.285,P＞0.05）.（4）预测因素分析：单因素Logistic回归分析发现RANSON评分、BISAP评分、miR-10b是影响PCD干预的因素（OR =4.170,5.612,2.500;95％可信区间：1.092 ～ 15.932,1.232 ～21.622,1.190 ～5.254,P＜0.05）.多因素Logistic回归分析发现miR-10b是急性胰腺炎PCD干预的独立影响因素（OR=2.374,95％可信区间：1.115 ～5.056,P＜0.05）.结论 miR-10b与miR-146a可能成为判断急性重症胰腺炎严重程度的预测指标;miR-10b可能成为急性胰腺炎是否行PCD干预的判定指标.

Objective To predict the severity of acute pancreatitis by detecting the changes of microRNA in the serum,and whether paracentesis catheter drainage （PCD） should be applied to the patients.Methods The peripheral blood of 120 patients with acute pancreatitis who were admitted to the General Hospital of Chengdu Military Command from October 2013 to March 2014 were collected.Thirty-five patients with severe acute pancreatitis （SAP） or moderately severe acute pancreatitis （MSAP） were in the group A,and 85 patients with mild acute pancreatitis （MAP） were in the group B.The scores of the acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ）,RANSON and bedside index for severity in acute pancreatitis （BISAP） were assessed.The expressions of the miR-146a,miR-10b,miR-21 and miR-26a in the serum were detected by the real-time quantitative PCR.The differences in the expressions of the 4 kinds of microRNAs in the 2 groups were compared,and the correlation between the 3 exaluation system was analyzed.Factors influencing the timing of the PCD for the PCD patients were analyzed.The measurement data were analyzed using the t test,and the relationship between the variables was analyzed using the linear correlation analysis or the rank correlation analysis.Univariate or multivariate analysis was done by the Logistic regression analysis.Results （1） The scores of the APACHE Ⅱ,RANSON and BISAP were 8.28 ±0.61,3.42 ±0.54 and 1.71 ±0.32 in the group A,and 3.18 ±0.52,1.43 ±0.25 and 0.37 ±0.06 in the group B,with significant differences between the 2 groups （t =4.266,7.809,4.113,P ＜ 0.05）.（2） The expressions of the miR-146a,miR-10b,miR-21 and miR-26a were 1.41 ± 0.21,2.94 ± 0.49,1.62 ± 0.25,1.21 ± 0.20 in the group A,and 6.29 ± 0.91,0.52 ± 0.09,2.82 ± 0.33 and 3.57 ± 0.64 in the group B.There were significant differences in the expression of the miR-146a and miR-10b between the 2 groups （t＝-2.156,2.110,P ＜0.05）,while no significant difference in the miR-21,miR-26a was detected between the 2 groups （t =-1.114,-1.571,P ＞ 0.05）.（3） There was correlation between the expressions of the miR-146a,miR-10b and the APACHE Ⅱ,RANSON,BISAP in the group A （r =-0.826,0.837,-0.874,0.866,-0.833,0.899,P ＜ 0.05）,while no correlation was detected between the expressions of the miR-21,miR-26a and the 3 exaluation systems in the group A （r =0.642,0.321,0.701,0.750,0.716,0.716,P ＞ 0.05）.There was no significant difference between the miR-146a,miR-10b,miR-21,miR-26a and the APACHE Ⅱ （r =0.067,0.347,0.133,0.111,P＞0.05）,RANSON （r=0.178,0.078,0.092,0.142,P ＞0.05） and BISAP （r =0.103,0.260,0.216,0.285,P ＞ 0.05） in the group B.（4） The results of univariate analysis showed that miR-10b,RANSON and BISAP were the factors influencing the timing of PCD （OR =4.170,5.612,2.500,95 ％ confidence interval：1.092-15.932,1.232-21.622,1.190-5.254,P ＜ 0.05）.The results of multivariate analysis showed that miR-10b was the factor influencing the timing of PCD （OR =2.374,95％ confidence interval：1.115-5.056,P ＜ 0.05）.Conclusions miR-10b and miR-146a might be the predictors of severity of severe acute pancreatitis; miR-10b might be the indicator in judging whether PCD should be applied.