黄芪水提物对阿霉素肾病大鼠ANP抵抗的改善作用及其机制研究

Astragali radix extract ameliorates renal resistance to atrial natriuretic peptide in rats with experimental nephrotic syndrome

目的:研究黄芪水提物(ARE)对阿霉素肾病大鼠心房利钠肽(ANP)抵抗的影响,并探讨其机制。方法:雄性SD大鼠随机分为正常对照组、阿霉素肾病模型组(ADR)、ADR+黄芪水提物(2.5g·kg-1.d-1)组及ADR+苯那普利(10mg·kg-1.d-1)组。用药6周后观察大鼠在2%体重生理盐水扩容情况下的利钠反应、血浆ANP的浓度、尿环鸟苷酸(cGMP)排泄量(UcGMPV)、肾内髓组织磷酸二酯酶5(PDE5)活性及蛋白表达水平。结果:ADR大鼠扩容后,尽管血浆ANP水平较正常大鼠明显增加,其利钠反应和UcGMPV却显著降低(P<0.01)。ARE能部分恢复大鼠扩容利钠反应,显著增加尿钠排泄量(UNaV)及UcGMPV(P<0.01)。ARE明显抑制肾内髓组织PDE5活性[(6.8±0.8)nmol.g-1.min-1vs(9.9±1.1)nmol.g-1.min-1,P<0.01]及蛋白表达(1.0±0.1vs1.4±0.2,P<0.01)。结论:ARE能显著改善阿霉素肾病大鼠ANP抵抗,其机制可能与其抑制PDE5活性及蛋白表达有关。

AIM： To study the effects of astragali radix extract （ARE） on renal resistance to atrial natriuretic peptide （ANP） in rats with experimental nephrotic syndrome. METHODS： Male Sprague -Dawley rats were randomly divided into normal control, adriamycin nephropathy （ADR）, ADR treated with ARE （2. 5 g · kg^-1· d^-1 ） and ADR treated with benazepril （10 mg· kg^-1· d^-l）. After 6 weeks, rats received intravenous infusion of 2% body weight isotonic saline. Urinary cGMP excretion （UeGMpV） , plasma ANP level, renal PDE5 activity and protein expression were also detected. RESULTS- ARE increased UNaV while ACEI was not natriuretic. Nephrotic rats had a blunted natriuretic response and reduced rate of UcGMpV after volume expansion despite higher plasma ANP concentration. ARE increased UoGMPV and restored partly natriuretic response to volume expansion. The activity and protein abundance of renal PDE5 were high in nephrotic rats. ARE significantly reduced the PDE5 activity and protein expression. CONCLUSION： ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDES.