摘要
目的探索并建立一种基于循环micro RNA的诊断大鼠溃疡性结肠炎(ulcerative colitis,UC)方法并监测其治疗后效果的临床前策略。方法第1阶段:硫酸葡聚糖(Dextran sulfate sodium,DSS)诱导大鼠UC模型。实时定量RT-PCR筛选差异性的血清micro RNA。ELISA检测血清核周抗中性粒细胞胞浆抗体(periunclear antineutrophil cytoplasmic antibodies,p ANCA)。Logistic回归法建立诊断模型Indice。受试者工作特征(receiver operating characteristic,ROC)曲线评价指标的诊断效能。第2阶段:验证指标对UC的诊断效能,并用其评价UC的疗效。结果第1阶段:大鼠UC模型建立成功。Mi R-20b、mi R-21和let-7e*在UC大鼠血清中高表达,mi R-125b-1*无明显变化。p ANCA在UC大鼠血清中高表达。诊断模型Indice=0+(2.645×mi R-20b)+(1.622×mi R21)+(0.979×let-7e*)+(0.082×p ANCA)的诊断效能强于各单项指标。第2阶段:各指标均能监测UC疗效,Indice的监测效能最强。结论循环micro RNA能稳定高效的诊断UC并监测其治疗后效果。
This study aimed to explore and establish a preclinical strategy for diagnosis and therapeutic following of rat ulcerative colitis based on circulating microRNA. First stage： rat ulcerative colitis was induced by dextran sulfate sodium （DSS）. Differentially expressed serum microRNAs were screened and validated by review of literature and real-time RT-PCR, while serum pANCA was tested by ELISA. Then combinative diagnostic Indice was established using logistic regression model based on the data from first stage. The diagnostic performance, including AUC, specificity, sensitivity and Youden index, were evaluated by receiver operating characteristic （ROC） analysis. Second stage： the diagnostic performance of combinative indice were validated in this stage, and the indice was further used for evaluation of therapeutic effect on ulcerative colitis. Data showed that rat ulcerative colitis model was successfully established. MiR-20b, miR-21 and let-7e＊ were up-regulated in the serum of ulcerative colitis rats, whereas miR-125b-l＊ showed no difference; serum pANCA was also up-regulated in the ulcerative colitis rats. The diagnostic performance of the established Indice = 0＋ （2.645xmiR-20b）＋ （1.622×miR21）＋ （0.979× let-7e＊） ＋ （0.082 × pANCA）, which was much better than other individual markers. All the individual markers and Indice could be used effectively for surveillance of ulcerative colitis therapeutic effect, and among them Indice was the most efficient. In conclusion, circulating microRNAs is able to stably and efficiently diagnose rat ulcerative colitis and further to follow up on therapeutic effect.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2017年第6期530-536,共7页
Immunological Journal
基金
重庆市自然科学基金(CSTC2014jcyj A10055)
重庆市渝北区科委项目(渝北财教[2013])
