Nexilin 作为一个新的心力衰竭生物标志物的研究

Heart failure is a complex clinical syndrome, early diagnosis of heart failure, risk stratification and prognostic evaluation is still a problem..Biomarkers as a tool for diagnosis and prognostic evaluation of heart failure has been widely applied, where B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are excellent biomarkers, however, given the complexity of this syndrome it is unlikely that these biomarkers will be adequate, and additional measures that capture newly identified aspects of heart failure may improve diagnosis, risk stratification and assessment of adverse outcomes..Nexilin was isolated previously as a novel actin filament binding protein localized at cell-matrix adherens junctions, recently research data has shown that Nexilin is highly abundant in the heart and skeletal muscle, and is located specifically to the Z-disc, loss of nexilin in zebrafish led to perturbed Z-disc stability and heart failure. Human genetic association study on individuals with dilated cardiomyopathy found several mutations in Nexilin associated with the disease..The purpose of this study is to investigate the application value of nexilin as heart failure biomarkers. By constructing rat model of heart failure, clarify the characteristics of Nexilin expression in the heart failure processing and the release mechanism of Nexilin. Through the detection of serum Nexilin level in patients with acute and chronic heart failure, explore Nexilin sensitivity and specificity as biomarkers for diagnosis of heart failure, as well as the relationship between serum Nexilin level and adverse outcomes. .This study will provide useful clues of diagnosis and prognosis of heart failure， while it is helpful to the new pathogenesis, therapeutic targets of heart failure, as well as further study of Nexilin function..

心力衰竭是一个复杂的临床综合征，早期诊断、分级以及预后评估仍是个难题。生物标志物作为心衰诊断和预后评估的手段已被广泛应用，其中B型利钠肽(BNP)和N末端BNP(NT-proBNP)是较可靠的指标，但尚不能满足临床需要，寻找新的心衰生物标志物仍然是当前研究的热点。Nexilin是一个肌组织特异、高丰度表达的新基因，最近的研究表明Nexilin缺失导致心力衰竭。为探讨Nexilin作为心衰生物标志物的可行性，本研究拟通过构建大鼠心衰动物模型，研究Nexilin在心衰过程中的表达特点和血浆Nexilin的释放机制；通过检测急性和慢性心力衰竭患者血清Nexilin水平，探讨Nexilin作为心力衰竭诊断标志物的特异性和灵敏度，以及血清Nexilin水平与不良预后的关系。本研究将为心力衰竭的诊断和预后评估提供有价值的线索，同时对心力衰竭的发病机制、治疗靶点以及Nexilin基因功能研究提供帮助。

心力衰竭是一个复杂的临床综合征，早期诊断、分级以及预后评估仍是个难题。生物标志物作为心衰诊断和预后评估的手段已被广泛应用，其中B型利钠肽(BNP)和N末端BNP(NT-proBNP)是较可靠的指标，但尚不能满足临床需要，寻找新的心衰生物标志物仍然是当前研究的热点。Nexilin是一个心脏高丰度表达的新基因，研究表明Nexilin缺失导致心力衰竭，本研究探讨了Nexilin作为心衰生物标志物的可行性。本项目研究结果显示，高血压、冠心病、扩心病导致的慢性心衰患者血清Nexilin含量均明显高于对照组(P<0.001)，血清Nexilin区分心衰的ROC曲线下面积分别为为0.663、0.604和0.975；血清Nexilin含量随着心功能分级升高亦明显升高(P<0.001)；随访1年，Nexilin高含量组慢性心衰患者再入院和死亡不良事件发生率明显高于低含量组(P<0.05)。急性心衰组血清Nexilin明显高于对照组(P<0.001)，经过1年的随访，结果死亡组血清Nexilin含量明显高于对照组(P<0.05)。心力衰竭动物实验显示心衰组血清Nexilin含量明显增加(P＜0.001)。健康成人血清Nexilin含量检测显示男性明显高于女性，并且与年龄呈明显的相关趋势。我们还发现，急性缺血性脑卒中患者与健康成人对照组比较，血清Nexilin含量明显升高(P<0.001)；急性冠脉综合症患者血清Nexilin含量分析表明心肌梗死(AMI)患者血清Nexilin含量明显高于对照组 (P <0.001)，不稳定心绞痛(UA)患者血清Nexilin含量亦明显高于对照组 (P <0.001)；胶质瘤组织Nexilin表达明显高于非肿瘤组织(P<0.001)。我们的研究提示血清Nexilin水平可能是心力衰竭的一个诊断、危险分层和预后的有用生物标志物。