养心颗粒改善心力衰竭大鼠模型水钠潴留的作用机制研究

Mechanism of Yangxin Granule on Reducing Water and Sodium Retention in Heart Failure Rats

目的研究养心颗粒对心力衰竭大鼠模型水钠潴留的作用机制。方法SD大鼠70只,除空白对照组(10只)外,其余60只采用连续腹腔注射阿霉素的方法复制大鼠心力衰竭模型,选取具有水钠潴留症状的大鼠48只,随机分为模型对照组、养心颗粒治疗组(高剂量组、中剂量组、低剂量组)与阳性对照组,养心颗粒治疗组给予不同剂量养心颗粒治疗,阳性对照组给予托伐普坦治疗,8周后观察大鼠体重及尿量、尿钠、尿渗透压的变化,测定血清N末端B型利钠肽原(NT-proBNP)、血管加压素(AVP)、AVPV2受体(AVPV2R)、环磷酸腺苷(cAMP)、环磷酸腺苷交换蛋白1(Epac1)和尿液水通道蛋白-2(AQP2)水平。结果养心颗粒能对抗阿霉素对心脏的毒性反应。与模型对照组比较,养心颗粒各剂量组与阳性对照组大鼠尿量、尿钠、尿渗透压水平增加,水钠潴留减轻;血清NT-proBNP、AVP、AVPV2R、cAMP及尿液AQP2的水平降低,心肌组织cAMP、Epac1及肾脏组织AQP2的表达水平降低。结论养心颗粒能够通过抑制AVP-cAMP-Epac1-AQP2通路核心分子的表达,从而减轻水钠潴留,这可能是该药治疗心力衰竭的作用机制之一。

Objective To investigate the mechanism of Yangxin Granule on water and sodium retention in heart failure rats.Methods Seventy SD rats were selected.Except for the blank group(n=10),adriamycin was given intraperitoneally to 60 SD rats to establish the model of heart failure.The rats with symptoms of retention of water and sodium were selected and divided into model group,Yangxin Granule treating group(high dose group,middle dose group,and low dose group),and positive control group.The rats in Yangxin Granule treatment group were given different doses of Yangxin Granule,the rats in positive control group were treated with torvalputan.After 8 weeks of treatment,the changes of body weight,urine volume,urine sodium,and urine osmotic pressure were observed.The levels of N-terminal fragment of proB-type natriuretic peptide(NT-proBNP),vasopressin(AVP),AVPV2R,cyclic adenosine monophosphate(cAMP),exchange protein activated by cAMP(Epac1)in serum and aquaporin-2(AQP2)in urine were detected.The expression of cAMP and Epac1 in myocardium and AQP2 in kidney were detected by immunohistochemistry.Results Yangxin Granule reduced the toxic reaction of adriamycin to heart.Compared with model control group,urine volume,urinary sodium,and urine osmolarity increased,retention of water and sodium reduced,the levels of NT-proBNP,AVP,AVPV2R,cAMP,Epac1 in serum and AQP2 in urine decreased,and the expression of cAMP,Epac1 in myocardial tissue and AQP2 in kidney tissue reduced in each dose group of Yangxin Granule.Conclusion Yangxin granule can significantly inhibit the expression of AVP-cAMP-Epac1-AQP2 pathway core molecules and thus reduce the retention of water and sodium,which may be one of the mechanisms in treating heart failure.