重组人松弛素对舒张性心力衰竭模型兔心肌组织蛋白激酶G活性的调控

Effect of recombinant human relaxin on regulating protein kinase G in myocardial tissue taken from a rabbit diastolic heart failure model

目的探讨重组人松弛素(RLX)对舒张性心力衰竭(DHF)模型兔心肌组织蛋白激酶G(PKG)活性的调控作用。方法采用腹主动脉缩窄术建立DHF模型兔,新西兰家兔28只随机分为假手术组6只、DHF组6只、RLX小剂量组8只[30μg/(kg·d)]、RLX大剂量组8只[98μg/(kg·d)],给药2周。术后第10周,取血清标本,分别采用ELISA法检测钠尿肽、RLX,制备10%心肌匀浆液样本ELISA法测3-硝基酪氨酸(3-NT)、NO、环磷酸鸟苷(cGMP)、PKG。结果与假手术组比较,DHF组、RLX小剂量组、RLX大剂量组血清钠尿肽、心肌匀浆3-NT水平明显升高,NO、cGMP、PKG活性明显降低,差异有统计学意义(P<0.05)。与DHF组比较,RLX大剂量组心肌匀浆中NO、cGMP、PKG活性明显升高[(18.70±0.27)μmol/L vs(16.38±0.16)μmol/L,(10.63±0.34)nmol/L vs(9.15±0.27)nmol/L,(528.58±3.66)U/L vs(493.26±5.68)U/L,P<0.05],3-NT水平明显降低[(239.98±2.75)μmol/L vs(261.79±4.48)μmol/L,P<0.05]。结论大剂量RLX减轻家兔左心室舒张功能可能是通过NO-cGMP-PKG通路减轻DHF模型兔氧化应激反应,提升NO生物学利用度、PKG活性,从而拮抗心肌纤维化,进而减轻左心室的舒张功能障碍。

Objective To study the effect of recombinant human relaxin（RLX）on regulating the protein kinase G（PKG）in myocardial tissue taken from a rabbit diastolic heart failure（DHF）model.Methods A DHF model of rabbits was established by constricting their abominal aorta.Twenty-eight New Zealand rabbits were randomly divided into sham operation group（n=6）,DHF group（n=6）,30μg/kg·d RLX group（n=8）,98μg/kg·d RLX group（n=8）.The animals were treated with RLX for 2 weeeks.Serum samples were taken at week 10 after operation for measuring the serum levels of BNP,RLX,3-NT,NO,cGMP and PKG by ELISA.Results The serum levels of BNP and 3-NT were significantly higher while those of NO,cGMP and PKG were significantly lower in DHF group,30μg/kg·d RLX group and 98μg/kg·d RLX group than in sham operaion group（P〈0.05）.The serum levels of NO,cGMP and PKG were significantly higher while those of 3-NT were significantly lower in 98μg/kg·d RLX group than in DHF group（P〈0.05）.Conclusion Large RLX dose alleviates the left ventricular diastolic function and oxidative stress,increases the bioavailability of NO and the activity of PKG through the signal pathaway of NO,cGMP,PKG,and can thus prevent myocardial fibrosis and improve the left ventricular diastolic function in DHF rabbits.