琼西地区精神分裂症患者血浆MiR-137,MiR-181b及MiR-132表达及其相关性研究

目的 探讨microRNA-137(MiR-137),microRNA-181b(MiR-181b)及microRNA-132(MiR-132)表达水平在琼西地区精神分裂症患者抗精神病药物治疗过程的变化及相关性。方法 选取琼西地区386例精神分裂症患者(病例组)和106例健康体检者(对照组),采用实时荧光定量PCR检测两组血浆MiR-137,MiR-181b及MiR-132表达水平。在病例组中选阳性与阴性症状量表(PANSS)分>70分的104例患者(观察组),于治疗前、治疗14天、治疗30天、治疗50天分别检测MiR-137,MiR-181b及MiR-132表达水平,并采用PANSS,大体评定量表(GAS)和病情严重程度量表(SI)对不同治疗阶段的临床症状及疗效进行评估。结果 与对照组比较,病例组MiR-181b及MiR-132表达水平显著上调(Z=-3.315,P=0.001; Z=-2.036,P=0.038)。观察组治疗30天和50天血浆MiR-181b及MiR-132表达水平较治疗前及治疗14天显著下调(t=8.382～12.651,P<0.05),且观察组治疗50天血浆MiR-181b及MiR-132表达水平较治疗30天显著下调(t=7.695～12.824,P<0.05)。随着治疗时间延长观察组患者PANSS评分及SI评分显著降低(t=8.711～10.273,P<0.01),而随着治疗时间延长观察组患者GAS评分显著增高(t=7.523～12.861,P<0.01)。相关分析显示,与治疗30天比较,治疗50天病例组MiR-181b及MiR-132表达水平下调与GAS评分呈明显正相关(r=0.537,P<0.05; r=0.492,P<0.05); 治疗50d与治疗前比较,病例组MiR-181b及MiR-132表达水平的下调与PANSS评分呈明显负相关(r=-0.503,P<0.05; r=-0.516,P<0.05)。ROC曲线显示,MiR-181b的AUC是0.694(95%CI:0.527～0.875),敏感度和特异度为56.8%和78.3%; MiR-132的AUC是0.627(95%CI:0.474～0.788),敏感度和特异度分别为52.4%和71.9%。Logistic回归分析显示,MiR-181b具有显著相对危险度(OR=2.346,95%CI:1.363～4.145,P=0.026)。结论 MiR-181b及MiR-132表达水平与精神分裂症发生和病情转归有一定的相关性,MiR-181b可作为预测精神分裂症发生的危险因素。

Expression of Plasma MiR-137,MiR-181b and MiR-132 of Schizophrenia Patients in Qiongxi Area and Its Correlation Study

Objective To investigate microRNA-137(MiR-137),microRNA-181b(MiR-181b)and microRNA-132(MiR-132)expression levels inQiongxi area of schizophrenia patients with antipsychotic drug treatment process change and correlation.Methods Qiongxi area selected 386 cases of schizophrenia patients(case group)and 106 cases of healthy persons(control group)by real-time fluorescence quantitative PCR were used to detect the two groups of plasma MiR-137,MiR-181b and MiR-132 expression levels.104 cases of schizophrenia patients(observer group)with total score of Positive and Negative Syndrome Scale(PANSS)>70 were detected before treatment,treatment for 14 days,30 days of treatment and treatment for 50 days the expression levels of MiR-137,MiR-181b and MiR-132.By PANSS,global assessment scale(GAS)and severity of illness(SI)to evaluate the clinical symptoms and curative effect of different treatment stages of schizophrenia.Results Compared with the control group,the case group MiR-181b and MiR-132 wereup-regulated(Z=-3.315,P=0.001; Z=-2.036,P=0.038).The observer grouptreatment for 30 days and 50 days the expression of plasma MiR-181b and MiR-132 levels were significantly lower than before treatment and treatment for 14 days(t=8.382～12.651,P<0.05).The observer group treatment for 50 days the expression of plasma MiR-181b and MiR-132 levels than treatment for 30 dayssignificantly decreased(t=7.695～12.824,P<0.05).With the prolonging ofthe treatment time of patients in the observer group PANSS score and SI score were significantly decreased (t=8.711～10.273,P<0.01).With the prolonging of the treatment time of patients in the observer group GAS score was significantly increased(t=7.523～12.861,P<0.01).Correlation analysis showed that,with 30 days of treatment,treatment for 50 days in case group of MiR-181band MiR-132 levels downregulated were positively correlated with GAS score(r=0.537,P<0.05; r=0.492,P<0.05).50 days of treatment compared with before treatment,case group of MiR-181b and MiR-132 levels downregulated were negatively correlated with PANSS score(r=-0.503,P<0.05; r=-0.516,P<0.05).The ROC curve showed that the MiR-181b of AUC was 0.694(95%CI:0.527 to 0.875),the sensitivity and specificity were 56.8% and 78.3%。The MiR-132 ofAUC was 0.627(95%CI:0.474 to 0.788),the sensitivity and specificity were 52.4% and 71.9%.Logistic regression analysis showed that the MiR-181b has significant relative risk(OR=2.346,95%CI:1.363 to 4.145,P=0.026)。Conclusion MiR-181b and MiR-132 expression levels with schizophrenia incidence and disease outcome had some relevance,and MiR-181b can be used to predict risk factors of schizophrenic occurrence.