盆腔炎性疾病代谢物类型生物标志物的探索

Nowadays, it is a difficulty in the diagnosis of pelvic inflammatory disease (PID) with mild or no symptoms which is also named as subclinical PID by some researchers. Unfortunately, relevant studies showed that if subclinical PID did not be treated in time or completely, it will cause serious sequelae, such as ectopic pregnancy, infertility, etc. Researchers put efforts to seeking new methods for the diagnosis of subclinical PID, but the results are not satisfactory. Metabolomic studies can find metabolites with abnormal concentrations at the early stage of disease, and these metabolites can be used as biomarkers for the diagnosis of the disease especially in the asymptomatic period. However, metabolomic studies on PID have not yet been reported. After establishing PID rat model and conducting metabolomic study, we found that the concentrations of 18 metabolites in urine showed statistically differences compared with that in control rats. Among these metabolites, arachidonic acid, 2 - hydroxy butyric acid and acetic acid reflected pathological changes of PID from various angles, including inflammation, local environment and local physical changes, respectively. In this case, these abnormal metabolites could be used as a potential biomarker for the diagnosis of subclinical PID. On the basis of the previous results, compared to the metabolomic of other relative disease patients and healthy people, we aimed to confirm whether the above metabolites can be used as biomarker to facilitate the clinical diagnosis of subclinical PID and the clinical judgment of whether PID has been treated completely, and try to find other more sensitive and specific biomarkers.

症状不明显的盆腔炎性疾病(PID)的诊断目前存在困难，但是不对其进行及时治疗或治疗不彻底将会引起严重后遗症。学者们致力于寻找新指标以帮助该疾病的诊断，但是结果尚不理想。代谢组学研究能找出疾病早期机体内浓度异常的代谢物，而这些代谢物可作为生物标志物用于疾病在症状不明显状态下的诊断，但是PID代谢组学研究尚未见报道。课题组前期建立大鼠PID模型，通过代谢组学研究发现，与对照组比较，模型大鼠尿液中18种代谢物的浓度异常，其中花生四烯酸、2-羟基丁酸和乙酸从炎症反应、局部环境和局部生理变化等多个角度反映PID的病理变化，可以作为PID潜在生物标志物组。本项目拟在此基础上，以健康人群、其它类型炎症患者和症状类似疾病患者为对照，研究疾病导致的代谢变化过程，取证能否将该分子组合开发为用于PID诊断的生物标志物，并尝试找出其它更灵敏和特异的生物标志物，为症状不明显PID的诊断和治疗是否痊愈的判断提供帮助。

盆腔炎性疾病（PID）是常见的妇科疾病，数据显示其发病率约为15-20%。PID如果不能及时诊断和有效治疗，会引起严重的后遗症。症状不明显的亚临床PID尚没有较好的无创诊断方法，PID治疗后是否痊愈，也缺乏简单准确的判断指标。本项目主要为解决上述两种问题开展。.PID大鼠尿液的代谢组学研究发现大鼠体内代谢轮廓发生变化，差异代谢物包括花生四烯酸、2-羟基丁酸和乙酸等，从炎症反应、局部环境和局部生理变化等多个角度反映PID的病理变化。检测大鼠组织液匀浆液中的差异代谢物，结果与尿液中结果相互印证。对PID大鼠给药医院制剂盆炎灵，获得了良好的治疗效果，该过程中，大鼠体内的差异代谢物随着治疗过程的深入，其在体内的水平逐步恢复。.收集了亚临床PID患者、健康受试者、症状明显的PID患者的标本，进行代谢组学研究。尿液代谢组学研究结果发现，PID患者尿液中花生四烯酸和2-羟基丁酸也是差异代谢物，但其变化不如大鼠体内明显；另外，乙酸的水平变化不明显。血浆代谢组学研究结果表明，亚临床PID患者体内代谢存在明显的变化，涉及脂类物质代谢和酚类物质代谢，找到了11种差异代谢物，这些代谢物中溶血磷脂酸(16,0/0:0)有相对较高的AUC值，其灵敏度为89.3%，特异性为73.3%；差异代谢组建立的模型能够准确预测后续收集的16例未知标本。症状明显的PID患者，其代谢变化与亚临床PID无统计学差异，该变化可能与患者体内器质性病变的程度有关。患者在接受医院制剂的一个月疗程中，于第14天和28天收集其样本，结果表明治疗过程中差异代谢物的水平逐渐修复。子宫内膜异位症患者（无PID）体内的上述差异代谢物水平与健康受试者无统计学差异，表明差异代谢物有一定的PID特异性。.另外研究了亚临床PID患者体内T4多核苷酸激酶活性的变化，发现PID导致酶活性的降低，也可作为潜在的诊断方法。.该项目的科学意义在于发现PID导致的体内的差异代谢物组，该差异代谢物组可以作为潜在生物标志物，通过后续扩大样本和多中心研究后，用于亚临床PID的诊断和PID治疗进程的指标。