AC-NP:一种具有利尿钠、舒血管作用的新型钠尿肽

AC-NP:a novel peptide with natriuretic and vasorelaxing actions

目的评价AC-NP—一种新设计合成的钠尿肽(natriuretic,NP)的心血管活性和肾活性。方法将具有6个氨基酸的ANP(心房钠尿肽)C末端、5个氨基酸的ANP的N末端,以及具有17个氨基酸的CNP(C型钠尿肽)环结构,设计合成具有28个氨基酸的新型钠尿肽AC-NP。通过离体血管灌流方法、在体给药前后颈动脉压的监测并采用塞曼原子吸收光谱分析法测定尿钠变化、放射免疫法测定血浆及尿cGMP水平变化评价AC-NP的心血管活性及肾活性。结果在正常SD大鼠,相对于ANP、CNP及另一种人工合成的钠尿肽VNP(血管钠肽),AC-NP具有更强的利尿(P<0.05)、利钠(P<0.05)和降血压作用(P<0.05)。而对离体腹主动脉的舒张功能,AC-NP和ANP、CNP、VNP作用相当(P>0.05)。相对于生理盐水对照组,AC-NP显著升高血浆及尿cGMP水平(P<0.05),且尿cGMP水平的升高与CNP、VNP组的差异具统计学意义(P<0.05)。结论新型人工合成的钠尿肽AC-NP具有利尿钠、舒血管、降血压作用,这些作用的发挥可能通过传统的信号转导通路NPs/NPR/cGMP/PKG实现。AC-NP或许可作为临床上治疗心肾功能障碍的新的候选肽类药物。

Objective To evaluate the cardiovascular and renal activities of a newly designed natriuretic peptide（NP）. Methods A novel 28-amino acid chimeric peptide had been engineered,which combined the 17-amino acid ring of C type natriuretic peptide（CNP） with the 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide（ANP）.The cardiovascular and renal activities of AC-NP were evaluated by in vitro perfusion and in vivo record of carotid arterial pressure before and after administration of NPs.The levels of cGMP in plasma and urine were determined by radioimmunoassay and urine sodium excretion via Zeeman atomic Absorption spectroscopy. Results In normal SD rats,AC-NP proved to be more potentially diuretic,natriuretic and hypotensive compared with other NPs,such as ANP,CNP and vasonatrin peptide（VNP）（P0.05）,which is another man-made NP.In relaxation of isolated abdominal aorta from rat,AC-NP was equally effective to ANP,CNP and VNP（P0.05）.The levels of 3′,5′-guanosine monophosphate（cGMP） in plasma and urine were elevated by AC-NP compared with the normal saline（P0.05）.The levels of urine cGMP increased more by AC-NP than by CNP or VNP（P0.05）. Conclusion Innovative designed AC-NP might be a new candidate therapeutic peptide against cardiorenal disorders.