生物標幟物分子腦啡肽酶在心腎疾病應用的趨勢

腦啡肽酶 (neprilysin, NEP) 是含有鋅離子的II型膜蛋白的金屬內肽酶，是一個能調節人體重要內分泌的關鍵酵素。研究發現能通過抑制腦啡肽酶活性來減少利尿鈉肽降解，提高利尿鈉肽水平以改善血管內皮功能、抗動脈粥樣硬化、抗心肌纖維化、延緩心肌重構、改善心肌缺血、改善心臟功能等作用。心腎疾病在病理生理學傳統上被視為腎素-血管張力素-醛固酮系統 (Renin-Angiotension-Aldosterone System, RAAS)、交感神經系統 (Sympathetic Nervous System, SNS) 及細胞激素(Cytokine) 等系統不適當的活化，而導致一些生物活性分子，包括正腎上腺素、血管張力素II、內皮素-1、醛固酮、腫瘤壞死因子等的過度表達，進而造成心腎功能、血管內皮及組織結構的病變。因此研究抑制腦啡肽酶活性和外源性利尿鈉肽成為治療心腎疾病的神經內分泌拮抗治療策略，同時腦啡肽酶作為生物標幟物也是目前的研究重點，加強腦啡肽酶系統的生理效應將成為一種具有吸引力的替代治療方法。本文以文獻回顧方式，主要闡述腦啡肽酶在心腎疾病的臨床診治的應用趨勢，並探討腦啡肽酶與其他生物標幟物的相互關係。

Neprilysin (NEP) is a zinc-dependent type-II membrane-bound metallo-endoprotease which is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides. Resulting in natriuretic effects that are prone to improve endothelial function, reduce myocardial ischemia, produce a ventricular unloading, anti-atherosclerosis, anti-cardiac fibrosis, etc. Traditionally, the pathophysiological origins of cardio-renal disease have been viewed as the domain of the Renin-Angiotension-Aldosterone System (RAAS), Sympathetic Nervous System (SNS) and Cytokine system, with inappropriate activation of both systems leading to deleterious changes in cardio-renal function and structure. It is bioactive molecules, including norepinephrine, angiotensin-II, endothelin-1, aldosterone and tumor necrosis factor overexpression. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease and renal disease. And soluble NEP as biomarkers have also been investigated in heart failure trials and their predictive value are beginning to be recognized. Purpose of review to understand the role of neprilysin in cardio-renal disease and the relationship between NEP and other cardio-renal biomarkers.