血浆miRNA-1、miRNA-21对冠心病合并糖尿病患者PCI术后支架内再狭窄的影响

Effects of miRNA-1,miRNA-21 in plasma on in-stent restenosis in patients with coronary heart disease and diabetes mellitus after percutaneous coronary intervention

目的:观察血浆miRNA-1、miRNA-21在冠心病(CHD)与无冠脉病变患者中含量的差异,探讨其在CHD合并糖尿病(DM)患者的经皮冠状动脉介入治疗(PCI)后发生支架内再狭窄(ISR)与非支架内再狭窄(NISR)患者的含量差异及其对ISR的预测价值。方法:入选CHD支架置入术后患者(CHD组,n=187)、无冠脉病变患者(对照组,n=195)。根据指南,将对照组分为正常对照组(n=150)、单纯DM组(n=45);将CHD组分为单纯CHD组(n=119)、CHD合并DM组(n=68),又将CHD组分为ISR组(n=48)及NISR组(n=139);再将ISR组分为单纯ISR组(n=26)和ISR合并DM组(n=22)。收集各组患者血浆,提取总miRNA,检测miRNA-1、miRNA-21含量并分析各组的含量差异。结果:与对照组比较,CHD组miRNA-1、miRNA-21含量均升高(P<0.05);与NISR组比较,ISR组miRNA-1、miRNA-21含量均升高(P<0.05)。与单纯CHD组比较,CHD合并DM组ISR发生率明显升高;而且与单纯ISR组比较,ISR合并DM组miRNA-21含量升高(P<0.05),而单纯ISR组与ISR合并DM组miRNA-1含量无明显差异(P<0.05)。Logistics分析表明,与CHD患者相关危险因素DM、miRNA-1、miRNA-21的OR值分别为2.132,3.066,1.924(P<0.05,P<0.01); ISR患者相关危险因素DM、miRNA-21的OR值分别为3.091,5.654(P<0.05,P<0.01); CHD合并DM患者PCI术后发生ISR相关危险因素miRNA-21的OR值为9.148(P<0.01)。ROC曲线评价表明,miRNA-1,miRNA-21与CHD患者发生ISR的AUC分别为0.854,0.857; miRNA 21与CHD合并DM患者发生ISR的AUC为0.783。结论:血浆miRNA-1、miRNA-21对诊断CHD患者支架置入术后ISR发生有重要临床意义,miRNA-21对诊断CHD合并DM患者支架置入术后ISR发生尤其有重要临床意义。

Objective： To observe the expression differences of the plasma miRNA-1,miRNA-21 between patients with coronary heart disease（ CHD） and without coronary artery lesions,between patients with in-stent restenosis（ ISR） and none in-stent restenosis（ NISR）,and to study their predictive value for ISR occurred after percutaneous coronary intervention（ PCI） in patients with CHD and diabetes mellitus（ DM）. Methods： The selected subjects were divided into CHD group in which patients were implemented stenting（ n= 187）,and control group in which patients were without coronary artery lesions（ n = 195）. According to the guidelines,the control group was divided into normal group（ n = 150）,simple-DM group（ n = 45）; the CHD group was divided into simple-CHD group（ n =119） and CHD-DM group（ n = 68）,the CHD group was also divided into ISR group（ n = 48）,NISR group（ n = 139）,and the ISR group was divided into simple-ISR group（ n = 26） and ISR-DM group（ n = 22） again. Plasma was collected from each group,and total RNA was extracted,the level of blood miRNA-1,miRNA-21 of each group was detected,and their level differences were analyzed. Results： Compared with control group,the level of miRNA-1 and miRNA-21 of CHD group was increased（ P 0.05）; compared with NISR group,the level of miRNA-1 and miRNA-21 of ISR group was increased（ P〈0.05）. The incidence of ISR of CHD-DM group was obviously higher than that of simple-CHD group,ISR-DM group＇s level of miRNA-21 was higher than that of simple-ISR group（ P〈0.05）,and there was no difference of miRNA-1 level between ISR and ISR-DM group（ P〈0.05）. In Logistics,for CHD patents,the OR of DM,miRNA-1,miRNA-21 were 2.132,3.066,1.924 respectively（ P〈0.05）; for CHD patents with ISR,the OR of DM,miRNA-21 were 2.123,3.066 respectively（ P〈0.05）; especially for CHD and DM patents with ISR,the OR of miRNA-21 was 9.148（ P〈0.05）. In ROC curve,for CHD patients with ISR,the AUC of miRNA-1,miRNA-21 were 0.854,0.857 respectively; for CHD-DM patients with ISR,the AUC of miRNA-21 was 0.783. Conclusion： To predict the occurrence of ISR for CHD patients,the plasma miRNA-1 and miRNA-21 have a relatively high specificity and sensitivity,for CHD patients with DM,miRNA-21 may have a higher clinical value.