萘哌地尔对慢性心力衰竭患者神经内分泌的影响

The Effect of Naftopidil on the Neuroendocrine of Patients with Chronic Heart Failure

目的:观察萘哌地尔治疗慢性心力衰竭(CHF)患者时对神经内分泌的影响。方法:放射免疫法测定47例CHF患者(CHF组)与24例健康者(对照组)血肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、内皮素-1(ET-1)、肾上腺髓质素(Adm)、神经肽Y(NPY)、降钙素基因相关肽(CGRP)、A型利钠肽(ANP)、B型利钠肽(BNP)和C型利钠肽(CNP)的水平,超声心动图测定左室射血分数(LVEF)。CHF组再随机分为:常规治疗组(A组)24例,给予常规心衰治疗;萘哌地尔治疗组(B组)23例,在A组药物治疗基础上加服萘哌地尔,1月后重复上述测定。结果:(1)CHF患者血TNF-α,IL-1,IL-6,ET-1,Adm,NPY,ANP,BNP,CNP水平均显著高于对照组(P<0.01),而CGRP水平显著低于对照组(P<0.01);(2)A组和B组治疗前后比较,血TNF-α,IL-1,IL-6,ET-1,Adm,NPY,ANP,BNP,CNP水平均显著降低(P<0.01),而CGRP水平增高(P<0.01);(3)B组治疗后与A组治疗后比较,TNF-α,ET-1,ANP,BNP降低更明显(P<0.05),NPY水平下降更显著(P<0.01),而CGRP水平升高更明显(P<0.05),NYHA分级改善更明显(P<0.05),但IL-1,IL-6,Adm,CNP和LVEF无显著差异(P>0.05)。(4)LVEF与TNF-α,IL-6,ET-1,BNP呈负相关(P<0.05)。结论:TNF-α,IL-1,IL-6,ET-1,Adm,NPY,CGRP,ANP,BNP和CNP可能与CHF发生发展有关,萘哌地尔治疗可能进一步降低CHF患者TNF-α,ET-1,ANP,BNP,NPY水平和提高CGRP水平并改善临床症状。

Objective： To investigate the effect of naftopidil on the neuroendocrine of patients with chronic heart failure（CHF）. Methods： The levels of tumor necrosis factor-α （TNF-α） , interleukin-1 （ IL-1 ） , interleukin-6 （ IL-6 ）, endothelin-1 （ ET-1 ）, adrenomedullin （ Adm ）, neuropeptide Y （ NPY）, calcitonin gene-related peptide （ CGRP）, atrial natriuretic peptide （ ANP）, brain natriuretic peptide （BNP） and C-type natriuretic peptide （CNP） of 47 patients with CHF （CHF group） and 24 healthy subjects （control group） were tested by using radioimmunoassay, and their left ventricular fraction （LVEF） was measured with echocardiography respectively. The patients were randomized to receive naftopidil （50 mg Bid） in addition to routine therapy （group B, n = 23 ） or routine therapy only （ group A, n = 24） for one month. Results： 1. The levels of TNF-α, IL-1, IL-6, ET-1, Adm, NPY, ANP, BNP and CNP of the CHF groups were higher （P 〈0.01 ） and the level of CCRP was lower than those of control group （ P 〈 0.01 ）. 2. The levels of TNF-α, IL-1, IL-6, ET-1, Adm, NPY, ANP, BNP and CNP in groups A and B decreased significantly, and level of CGRP increased after the treatment than before （ P 〈 0. 01 ）. 3. Compared with those in group A after one month of treatment, the levels of TNF-α, ET-1, ANP, BNP and NPY in group B were even lowered （respectively P 〈 0.05 or P 〈 0.01 ）, and the level of CGRP was increased （ P 〈 0.05 ）, and NYHA functional class was improved （ P 〈 0.05 ）. But there were no differences （ P 〉 0.05 ） in the levels of IL-1, IL-6, Adm, CNP and LVEF. 4. There were significant inverse correlations between LVEF and TNF- α, ET-1, IL-6 or BNP levels （ P 〈 0.05 ）. Conclusions ： These findings suggest that TNF-α, IL-1, IL- 6, ET-1, Adm, NPY, CGRP, ANP, BNP and CNP could play important roles in CHF. Naftopidil could further decrease the levels of TNF-α, IL-6, ET-1, NPY, ANP and BNP, increase the level of CGRP, and improve the symptoms of CHF.