重组人心房肽对高血压大鼠心肌肥大的抑制作用及其机制

Suppressive effects of recombinant human atrial natriuretic peptide on myocardiac hypertrophy in hypertensive rats and its mechanisms

目的观察重组人心房肽(rhANP)对高血压大鼠心肌肥大的治疗效果,并探讨其作用机制。方法建立两肾一夹(2K1C)高血压大鼠模型,通过在高血压大鼠腹腔植入微囊化人心房肽cDNA重组质粒转染细胞,形成稳定的体内心房肽给药系统。检测假手术正常血压对照组、高血压模型组r、hANP治疗组大鼠的尾动脉收缩压(SBP)、血浆rhANP水平、心肌血管紧张素II(AngII)含量、心肌重量指数(MWI)、左心室肥厚指数(LVWI)、心肌胶原含量和心肌纤维直径等指标。结果rhANP治疗组大鼠的血浆rhANP浓度为217.3±11.3ng.L-1,显著高于另两组;高血压组大鼠的SBP、心肌AngII含量、MWI、LVWI、心肌胶原含量和心肌纤维直径较对照组显著增加(P<0.01)。rhANP治疗45d后显著降低高血压大鼠SBP、MWI、LVWI、心肌胶原含量、心肌纤维直径和心肌AngII含量(P<0.01)。结论由微囊化rhANPcDNA质粒转染细胞产生和分泌的rhANP可抑制心肌细胞肥大及胶原增生,有效防治左室肥厚,此作用与rhANP降低高血压大鼠的血压和心肌AngII含量有关。此结果也为高血压的心房肽基因治疗提供了新途径。

OBJECTIVE To investigate suppressive effects of recombinant human atrial natriuretic peptide （rhANP） on myocardiac hypertrophy in hypertensive rats and its possible mechanisms. METHODS Two- kidaaey,one- clip （2KIC） rats were used to establish the model of hypertension. The sustained - release system of rhANP in vivo was fabricated by implanting encapsulated rhANP cDNA plasmid transfected cells into 2KIC hypertensive rats intraperitoneally. Systolic blood pressure（SBP）, plasma rhANP level, AngⅡ content in myocardium, myocardium weight index （MWI）,left ventricular weight index （LVWI）, myocarudial collagen content and myocardial fiber diameter were determined among control group, hypertension group and rhANP group. RESULTS The concentration of rhANP in plasma was 217.3 ± 11.3 ng. L^-1 in rhANP group, higher than that in control group and hypertension group（ P 〈 0.01 ）. Compared with control group, the SBP, AngⅡ content in myocardium,MWI, LVWI,myocardial collagen content and myocardial fiber diameter were significantly increased in hypertension group（ P 〈 0.01 ）. rhANP had an obvious suppressive effect on the indices mentioned above（ P 〈 0.01 ）. CONCLUSION rhANP produced and secreted by encapsulated gene transfected cells can effectively suppress myocardial cell hypertrophy and collagenous fiber hyperplasia by decreasing blood pressure and myocardial AngⅡ content, thus play a role of suppressing myocardiac hypertrophy. It also provides a new rhANP gene therapeutic approach to hypertension.