Abstract研究背景： 尾加压素-II（urotensin II，U-II）是一种较内皮素-1更为强效的血管收缩肽，在动脉粥样硬化的发生、发展过程中起着重要作用。有研究证实，U-II可增加斑块稳定性，甚至逆转不稳定斑块，并对改善患者的预后具有一定作用。在心肌梗塞、心衰、高血压、糖尿病和动脉粥样硬化的患者及实验动物体内均可观察到血浆U-II和尾加压素受体（urotensin receptor, UT）水平的增高。且在急性冠脉综合征和心衰患者体内，U-II和炎症相关标志物C-反应蛋白（C-reactive protein, CRP）及脑钠肽成正相关关系。但目前有关UII在冠心病中，特别是急性冠脉综合征，中的作用及其仍需进一步探讨。 研究目的： 通过对急性心梗、不稳定心绞痛患者及健康志愿者血浆中U-II水平进行测定，同时将其与其它相关危险因素间的关系进行评估，以期探讨U-II在临床急性冠脉综合征诊疗过程中的价值及意义。 研究方法： 收集西安交通大学医学院第一附属医院心内科不稳定型心绞痛（UA）患者50例、急型心肌梗死（AMI）患者32例以及冠脉造影阴性者22例。冠心病严重程度用Gensini评分表示，血浆U-II水平用EIA法测定，并对血浆CRP, pro brain natriuretic peptide (Pro BNP), homeostasis model assessment of insulin resistance (HOMA IR), apo lipoprotein A (Apo A1), apo lipoprotein B (ApoB), total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), lipoprotein A (LPa) 的水平进行测定分析。 结果： 在本研究中，年龄，性别，body mass index（BMI） 和 腰围/臀围 在急型心肌梗死, 不稳定型心绞痛, 和对照组之间无显著差异。同样血浆TC, LDL, TG, Apo B, LPa, HDL, Apo A, LDL, Apo B, CRP, Pro-BNP水平的结果和射血分数跟别的研究人结果没有太大的不同造成的。 1. 急性心梗患者血浆U-II水平显著高于健康志愿者，并有统计学意义（333 pg/ml ? 269 pg/ml vs. 183 pg/ml ? 154 pg/ml, P < 0.05）；急性心梗组患者血浆UII水平虽有高于不稳定心绞痛组（313 pg/ml ? 286 pg/ml）的趋势，但统计学差异不明显。 2. 急性冠脉综合征患者中血浆UII水平与Gensini评分呈正相关（pearsons r = 0.285, P=0.003），并且与ApoB水平呈正相关（pearsons r = 0.23, P=0.015）。 3. 受试者工作特征（，ROC）曲线分析表明：U-II下的面积达到0.636（95％CI为0.473-0.789），与CRP（0.686，95％CI为0.512-0.861，P =0.352）接近。且CRP和U-Ⅱ（0.723）共同作用下的ROC比单独应用CRP有更高的曲线面积（P = 0.024）。 结论： 急性心梗患者血浆中UII水平显著升高，且其水平与冠心病严重程度、血浆ApoB水平及Gensini评分正相关。U-Ⅱ作为一个临床非侵入性生物标记物对ACS的早期诊断具有一定意义。
Background: Urotensin II (U-II) is a powerful vasoconstrictor peptide with potency greater than that of endothelin 1. Experimental and clinical studies have revealed that plasma level of U-II correlates positively with body weight. Increased expression of U-II and urotensin receptor (UT) has been found in animals with experimentally induced myocardial infarction, heart failure and in patients with hypertension, diabetes and atherosclerosis. Meanwhile, U-II has been found to be increased along with inflammatory markers like CRP in ACS patients and Pro BNP in the heart failure patients. Studies have also found that with the high level of plasma U-II there is slower deteriorations of cardiac function in heart failure patients with ESRD. U-II has been predicted to play role in converting unstable plaques to the stable plaques and it has been also found that the higher the U-II level, better the prognosis, in ACS. However, researches also predicted that U-II help in plaque formation by helping in foam cell formation. So far, U-II in patients with ACS is confusing and less known but surely has a potential role. Objectives: Plasma U-II level in patients with acute coronary syndromes (ACS) is still poorly understood. So, we sought 1) to determine plasma U-II levels and its correlated factors in acute coronary syndromes from Chinese Han population. 2) to investigate the diagnosis value of U-II in ACS, in order to complement the diagnostic biomarker in current clinical practices. Methods: Subjects were consecutively recruited from the inpatient and outpatient wards of the first affiliated hospital of Xi’an JiaoTong University school of medicine between April 2012 and September 2012. A total of 104 subjects after exclusion of 38 patients were enrolled and divided into three groups, acute myocardial infarction (AMI) 32 patients, unstable angina (UA) 50 patients and 22 cases of normal coronary angiography patients in Control group. The research protocol was approved by the Ethics Committee of Xi’an Jiaotong University. Informed consents were also obtained from all study subjects. Gensini score was calculated for the severity of coronary heart disease. Plasma U-II was measured by the enzyme immuno assay (EIA) according to the manufacturer’s instruction (Phoenix Pharmaceuticals, Inc., Belmont, CA).The lower limits of detection were 0.5 pg/mL. Each sample was carried out in duplicate by ELISA assay. Other biochemical measurements were performed by the central clincal laboratory of our hospital. Statistics and Analysis: Data are given as mean ± S.D. the differences among the groups were analyzed by one-way analysis of variance (ANOVA), followed by Post Hoc LSD method by using SPSS 13.0. Correlation analysis was performed using Pearson correlation among the parameters and the Uro- tensin II level. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis and the inter observer agreement was analyzed by weighted k statistics. Statistical signi?cance was assumed at the 5 % α-error level (P<0.05). Results: The age, gender, BMI, and Waist/Hip were no signi?cant differences among the con, UA and AMI groups and ejection fraction has no different result from others result. Biochemical Parameters In the present study, TC, LDL, TG, Apo B, LPa were not signi?cantly different among the groups. Our results regarding HDL, Apo A, LDL, Apo B, CRP, Pro-BNP were not much different from the others in suggesting the impaired lipid pro?le in ACS patients. Likewise, markers for the inflammatory conditions, CRP and the cardiac prognostic indicator, Pro-BNP were also not much different from others result. 1. Plasma U-II level in AMI group is significantly higher than in control group (333 ± 269 pg/ml vs.183 ± 154 pg/ml; P = 0.05) and insignificantly higher than in UA group (313 ± 286 pg/ml). Meanwhile, between UA group and control group, it was higher in UA group but statistically non significant. 2. Plasma U-II was positively correlated with Gensini score (r = 0.285, P = 0.003) and Apo B (r = 0.239; P = 0.015). 3. The ACS Diagnosis Value of Plasma U-II through receiver operating characteristic (ROC) curve: The area under the ROC curve for U-II reached to 0.636 (95 % CI 0.473–0.789) which was similar with ROC curve for CRP (0.686, 95 % CI 0.512–0.861, P = 0.352). Moreover, the area under the ROC curve for the combination of CRP and U-II (0.723) was signi?cantly higher than it for CRP alone (P = 0.024). Conclusions: Plasma U-II levels in patients with ACS are higher than healthy controls, which positively correlated with Gensini score and Apo B. The most important ?nding in our study is that plasma U-II increases the diagnostic value in ACS patient and may act as a clinical non-invasive biomarker for early diagnosis. The measurement of plasma U-II may provide further help in the risk strati?cation of subjects with ACS.