武汉云克隆科技股份有限公司

Abstract

Background: Inhibiting Neutral Endpeptidase-24.11 (NEP) combined with angiotensin receptor blocker (ARB) has recently been employed as an effective treatment for hypertension (HT). Although soluble form of NEP (sNEP) is able to measure in human plasma, the relationship between plasma levels of sNEP and clinical condition is still unknown in HT patients.

Methods: We consecutively measured plasma levels of sNEP and B-type natriuretic peptide (BNP) in 210 patients with HT (144 male, 66 female, mean age; 69.5±10.4) who were suspected cardiovascular disease with multiple risk factors from April 2013 to December 2013. The levels of plasma sNEP were measured by using commercially available ELISA kits (SEB785Hu, USCN life science inc.).

Results: Plasma levels of sNEP were non-normally distributed in whole high-risk HT patients assessed by Shapiro-Wilk test (p<0.01, median; 431.7 pg/ml, interquartile range; 302.0 to 540.9 pg/ml). sNEP levels were not significantly different among the patients with or without CAD [n=176, 431.7 pg/ml, (310.7 to 532.1) vs. n=34, 437.1 pg/ml, (284.4 to 574.6), p=0.851]. Plasma levels of sNEP were significantly greater in the HT patients treated with angiotensin converting enzyme inhibitors (ACEI) compared with those treated without ACEI [n=46, 493.4 pg/ml, (395.2 to 614.0) vs. n=164, 403.4 pg/ml, (299.6 to 523.8), p=0.012]. Plasma levels of sNEP were not significantly different between the patients with or without using ARB [n=107, 397.7 pg/ml, (284.8 to 506.8) vs. n=103, 456.4 pg/ml, (335.0 to 568.0), p=0.098]. There is no significant association between the plasma levels of sNEP and log BNP (ρ=0.018, P=0.801). Multivariable logistic regression analysis revealed that the administration of ACEI was independently associated with the higher levels of sNEP above median (odds ratio=2.48, 95% confidence interval; 1.23 to 5.03, p<0.02).

Conclusion: Among high risk patients with HT, patients treated with ACEI demonstrated significantly elevated levels of sNEP and the administration of ACEI was independently associated with the higher levels of sNEP. NEP could be up-regulated by ACEI and ARB did not significantly affect on NEP activity in HT patients. NEP could be effectively inhibited by a NEP-inhibitor in HT patients treated by ARB.

摘要

背景：抑制中性内肽酶-24.11（NEP）与血管紧张素受体阻滞剂（ARB）的结合最近被作为治疗高血压（HT）的有效方法。虽然可溶形式的NEP（sNEP）能够在人血浆中测到，但在高血压患者中，sNEP在血浆中的含量和临床条件之间的关系仍然是未知的。

方法：我们检测了210名高血压患者（144名男性，66名女性，平均年龄69.5±10.4）血浆中sNEP和B型钠肽（BNP）的含量，这些患者是从2013年4月到2013年12月有多种风险因素的疑似心血管疾病患者。我们用了商业化的ELISA kit（SEB785Hu，USCN life science inc.）检测了血浆中sNEP的含量。

结果：用Shapiro-Wilk test分析得出血浆sNEP的表达水平在高风险高血压患者中不正常分布（p<0.01，中值为431.7 pg / ml，四分位差为302.0到540.9 pg / ml)。在患有或未患冠心病的患者中，sNEP的水平并没有显著差异[n=176，431.7 pg/ml（310.7到532.1）和n=34，437.1 pg/ml（284.4到574.6），p=0.851]。在用血管紧张素转换酶抑制剂（ACEI）治疗的患者中，sNEP在血浆中的表达水平明显高于未用ACEI治疗的患者[n=46，493.4 pg/ml（395.2至614.0）与n=164，403.4 pg/ml（299.6至523.8），p=0.012]。在使用或不使用血管紧张素受体阻滞剂的患者中，sNEP在血浆中的表达水平没有显著差异[n=107，397.7 pg/ml（284.8到506.8）和n=103，456.4 pg/ml（335.0到568.0），p=0.098]。血浆中sNEP的表达水平和log BNP之间没有明显的联系（ρ=0.018，P=0.801）。多元logistic回归分析表明，ACEI的服用和较高水平的sNEP之间是独立相关的（优势比=2.48，95%置信区间；1.23 - 5.03，p < 0.02)。

结论：在高危高血压患者中，接受ACEI治疗的患者表现出明显较高的sNEP水平，而服用ACEI的患者与较高水平的sNEP独立相关。在高血压患者中，ACEI会上调NEP，ARB不会显著影响到的NEP活性。在用ARB治疗的高血压患者中，NEP抑制剂可以有效地抑制NEP。

使用试剂原文信息：The levels of plasma sNEP were measured by using commercially available ELISA kits (SEB785Hu, USCN life science inc.).