神经体液的因素在慢性心衰发生、发展中起关键作用，也是治疗的重要靶点，目前商品化的重组脑钠尿肽（rhBNP）治疗心衰取得了很好的疗效和经济效益，但半衰期仅22min，治疗费用昂贵，天然钠尿肽半衰期更短。我们与江南大学金坚教授合作，采用将BNP与人血清白蛋白（HSA）融合表达的策略延长BNP半衰期，开发了长效BNP，在小鼠体内测定半衰期为8h，体外实验表明长效BNP舒血管活性与天然BNP类似。我们近来研究VNP有升高APN，降低IL-6和ET-1等作用，上述作用的发现对课题的研究是有益的。本课题中我们以慢性心衰大鼠为研究对象，从整体、器官和细胞水平研究长效BNP对慢性心衰的治疗作用，从调节心脏/血管功能、心肌细胞钙瞬变、心肌细胞收缩力等方面探讨其机制，并测定APN、IL-6等细胞因子的变化，同时与商品化rhBNP的疗效进行比较，为长效BNP的临床应用提供实验依据。

Neural and hormonal regulation plays an important role in the process of choronic heart failure, and is also a therapeutic target. Recombinant brain natriuetic peptide (rhBNP) has been demostrated to have beneficial effects on the chronic heart failure, but its half-life is only 22 minutes. Natural natriuetic peptides have a shorter half-life than rhBNP. We have developed a long-acting BNP that has a longer half-life by fusion expression of BNP and human serum albumin. The half-life of our long-acting BNP is 8 hours in mice, and its effects on vasculature are similar with natural BNP. Our previous study have clarified that natriuetic peptides such as Vasonatrin peptide(VNP)，it reduced level of endothelin-1(ET-1), interlektin-6 (IL-6) and Angiotensin-Ⅱ(AngⅡ) and natriuetic peptide receptor-C(NRP-C) expression with increasing level of ANP and adiponectin (APN).In this poject, we will study the therapeutic effect of the novel BNP on chronic heart failure in rat, including the modulation of long-acting BNP on cardiac and vascular function, the contraction of cardiomyocytes and the calcium spark，and will detect the changes of APN and IL-6 in rats. We will also compare the effects of our novel BNP with the commercial rhBNP. The results will promote the translation of long-acting BNP into the clinic.