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人体内心钠素原N端片段的鉴定及其血浆浓度

Identification and plasma concentrations of the N-terminal fragment of proatrial natriuretic factor in man.

作者信息

Sundsfjord J A, Thibault G, Larochelle P, Cantin M

机构信息

Clinical Research Institute of Montreal, Quebec, Canada.

出版信息

J Clin Endocrinol Metab. 1988 Mar;66(3):605-10. doi: 10.1210/jcem-66-3-605.

DOI:10.1210/jcem-66-3-605
PMID:2965160
Abstract

A specific RIA was developed to measure plasma atrial natriuretic factor (ANF) N-terminal immunoreactivity in man. Antibodies raised in rabbits against a rat ANF N-terminal fragment [ANF-(11-37)] had 100% cross-reactivity with human ANF-(1-30) and purified plasma N-terminal ANF immunoreactivity. The ED80 and ED50 of standard curves prepared using [125I]human ANF-(1-30) and human ANF-(1-30) were 31.5 +/- 5.4 (+/- SD) and 132.5 +/- 20.4 fmol/tube, respectively. The plasma ANF N-terminal peptide concentrations were assayed directly, without extraction, since dilution of plasma and addition of standard to plasma yielded parallel dose-responses in the RIA and virtually 100% recovery of ANF-(1-30) added to plasma. Purification of ANF N-terminal immunoreactivity from 1.5 L human plasma by affinity chromatography and amino acid sequencing suggested that it was closely related to ANF-(1-98), although some degraded peptides were also detected. The mean basal plasma ANF N-terminal peptide level measured in 34 normal subjects was 420 +/- 157 (+/- SD) pmol/L. The values were higher in plasma from patients with congestive heart failure (grades III and IV; 7,041 +/- 6,136 pmol/L; n = 13) or chronic renal failure (10,079 +/- 4,942 pmol/L; n = 20). In 9 patients with chronic renal failure, hemodialysis resulted in a 30% (P less than 0.05) decrease in plasma ANF-(99-126) levels, from 34.7 +/- 12.3 (+/- SD) to 23.2 + 6.1 pmol/L, but no changes in plasma ANF N-terminal peptide concentrations. These data indicate that the N-terminal portion of pro-ANF is cosecreted with ANF-(99-126). Its higher plasma levels in the basal state and during chronic renal failure suggest a different process of elimination than that of ANF-(99-126), which may be partly mediated by the kidney.

摘要

已开发出一种特异性放射免疫分析法(RIA)来测定人血浆心房利钠因子(ANF)的N端免疫反应性。用针对大鼠ANF N端片段[ANF-(11 - 37)]免疫的兔抗体与人ANF-(1 - 30)及纯化的血浆N端ANF免疫反应性具有100%的交叉反应性。使用[125I]人ANF-(1 - 30)和人ANF-(1 - 30)制备的标准曲线的ED80和ED50分别为31.5±5.4(±标准差)和132.5±20.4 fmol/管。血浆ANF N端肽浓度无需提取即可直接测定,因为血浆稀释及向血浆中添加标准品在RIA中产生平行剂量反应,且添加到血浆中的ANF-(1 - 30)回收率几乎为100%。通过亲和层析从1.5 L人血浆中纯化ANF N端免疫反应性并进行氨基酸测序表明,它与ANF-(1 - 98)密切相关,尽管也检测到了一些降解肽段。在34名正常受试者中测得的基础血浆ANF N端肽平均水平为420±157(±标准差)pmol/L。充血性心力衰竭患者(III级和IV级;7041±6136 pmol/L;n = 13)或慢性肾衰竭患者(10079±4942 pmol/L;n = 20)血浆中的该值更高。在9名慢性肾衰竭患者中,血液透析导致血浆ANF-(99 - 126)水平降低30%(P<0.05),从34.7±12.3(±标准差)降至23.2 + 6.1 pmol/L,但血浆ANF N端肽浓度无变化。这些数据表明,前ANF的N端部分与ANF-(99 - 126)共同分泌。其在基础状态及慢性肾衰竭期间较高的血浆水平提示其清除过程与ANF-(99 - 126)不同,这可能部分由肾脏介导。

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