冠心病患者血清HOTAIR、SRSF1、mTOR通路标志物、NLRP3炎症小体及SIRI水平的相关性分析及对冠状动脉狭窄程度的预测价值

Correlation analysis of serum HOTAIR, SRSF1, mTOR-pathway markers, NLRP3 inflammasome and SIRI levels in patients with coronary heart disease and their predictive value for coronary stenosis severity

摘要:

目的]分析冠心病(CHD)患者血清HOX转录反义RNA(HOTAIR)、富丝氨酸和精氨酸的剪接因子1(SRSF1)、哺乳动物雷帕霉素靶蛋白(mTOR)通路标志物磷酸化真核翻译起始因子4E结合蛋白1/真核翻译起始因子4E结合蛋白1(p4EBP1/4EBP1)比值、NOD样受体蛋白3(NLRP3)炎症小体及全身炎症反应指数(SIRI)水平及相关性,并评估它们对冠状动脉狭窄程度的预测价值。 [方法]纳入2024年1月—12月在山西医科大学第二医院心内科收治的120例CHD患者(轻度、重度狭窄组各60例)和60例健康对照者。RT-qPCR检测血清HOTAIR水平,ELISA检测SRSF1、4EBP1、p4EBP1和NLRP3水平,计算SIRI,采用Gensini评分评估冠状动脉狭窄程度,采用Spearman相关、有序Logistic回归及ROC曲线分析标志物效能。 [结果]①重度狭窄组和轻度狭窄组血清HOTAIR、SRSF1、p4EBP1/4EBP1比值、SIRI较健康对照组显著升高(均P＜0.001)。NLRP3水平仅在重度组升高(P＜0.001)。②Spearman相关分析显示,各指标与冠状动脉狭窄程度之间均呈显著正相关关系,且各指标间亦呈正相关(均P＜0.001)；NLRP3水平与狭窄程度及其他指标呈正相关关系(P＜0.05),但与p4EBP1/4EBP1比值之间无显著相关性(P＞0.05)。③有序Logistic回归分析显示,上述指标升高均为冠状动脉狭窄程度的独立危险因素(P＜0.05)。④ROC曲线分析显示,各指标对冠状动脉重度狭窄均具有显著预测效能(均P＜0.001),且HOTAIR、SRSF1与SIRI水平的预测能力显著高于p4EBP1/4EBP1比值和NLRP3水平的预测能力。 [结论]冠心病患者血清HOTAIR、SRSF1、mTOR通路标志物、NLRP3及SIRI水平呈协同升高趋势,且与冠状动脉狭窄程度密切相关；HOTAIR、SRSF1与SIRI水平对冠状动脉重度狭窄具有高预测价值,为CHD的炎症机制研究和无创诊断提供了新方向。

Abstract:

Aim To analyze the levels and correlations of serum HOX transcript antisense RNA (HOTAIR), serine/arginine-rich splicing factor 1(SRSF1), mammalian target of rapamycin (mTOR) pathway markers phosphorylated eukaryotic translation initiation factor 4E binding protein 1/eukaryotic translation initiation factor 4E binding protein 1 (p4EBP1/4EBP1) ratio, NOD-like receptor protein 3 (NLRP3) inflammasome, and systemic inflammatory response index (SIRI) in patients with coronary heart disease (CHD), and to evaluate their predictive value for the severity of coronary stenosis. Methods During the period from January to December 2024, a total of 120 CHD patients (60 mild and 60 severe stenosis cases) and 60 healthy controls who received care in the Cardiology Department of the Second Hospital of Shanxi Medical University were recruited. Serum level of HOTAIR was measured by RT-qPCR, while SRSF1,4EBP1, p4EBP1, and NLRP3 levels were measured by enzyme-linked immunosorbent assay(ELISA). SIRI was calculated from the neutrophil, monocyte, and lymphocyte counts, the severity of coronary stenosis was evaluated using the Gensini scoring system. The efficacy of these biomarkers was assessed by Spearman correlation analysis, ordinal Logistic regression, and receiver operating characteristic (ROC) curve analysis. Results ①In severe stenosis group and mild stenosis group, serum levels of HOTAIR, SRSF1, p4EBP1/4EBP1 ratio, and SIRI were higher than those in healthy control group (all P＜0.001). In contrast, NLRP3 level increased only in the severe stenosis group(P＜0.001). ②Spearman correlation analysis revealed significant positive correlations between all measured biomarkers and the severity of coronary stenosis, as well as among the biomarkers themselves (all P＜0.001). NLRP3 level was positively correlated with stenosis severity and other biomarkers (P＜0.05), but not with the p4EBP1/4EBP1 ratio (P＞0.05). ③Ordinal Logistic regression analysis showed elevated levels of these biomarkers were all independent risk factors for the severity of coronary stenosis (all P＜0.05). ④ROC curve analysis demonstrated that all biomarkers had significant predictive efficacy for severe coronary stenosis (all P＜0.001), and the predictive ability of HOTAIR, SRSF1, and SIRI levels was significantly higher than that of the p4EBP1/4EBP1 ratio and NLRP3 level. Conclusion Serum levels of HOTAIR, SRSF1, mTOR pathway markers, NLRP3, and SIRI in patients with CHD show a coordinated elevation and are closely associated with the severity of coronary stenosis. HOTAIR, SRSF1, and SIRI demonstrate high predictive value for severe coronary stenosis, offering new insights into the inflammatory mechanisms and noninvasive diagnosis of CHD.