缬沙坦和螺内酯对高血压大鼠心肌生长因子和Ⅰ型胶原mRNA表达的影响

Effect of Valsartan and Spironolacton on Growth Factors and TypeⅠ Collagen in Left Ventricle in Spontaneously Hypertensive Rat

目的 观察血管紧张素Ⅱ (AngⅡ )AT1 受体拮抗剂缬沙坦和盐皮质激素受体拮抗剂螺内酯对自发性高血压大鼠 (SHR)左心室生长因子和Ⅰ型胶原mRNA表达的影响。方法 将 1 8只雄性SHR随机分为三组 :SHR对照组、缬沙坦治疗组、螺内酯治疗组 ,每组 6只。其中两治疗组分别用缬沙坦 30mg·kg- 1 ·d- 1 、螺内酯 2 0mg·kg- 1 ·d- 1 溶于饮水灌胃 ,每天一次 ,连续治疗 1 3周 ;另一组给正常饮水。另选同源同系Wistar kyoto大鼠 6只作为正常对照组。用RT PCR方法检测大鼠心肌转化生长因子 β1 (TGFβ1 )、肝细胞生长因子 (HGF)、Ⅰ型胶原mRNA水平。结果 治疗1 3周后 ,缬沙坦组和螺内酯组TGFβ1 、Ⅰ型胶原mRNA水平明显低于SHR对照组 (P <0 0 1 ) ,但高于WKY组 (P <0 0 1 ) ,其中螺内酯组Ⅰ型胶原mRNA水平高于缬沙坦组 (P <0 0 1 ) ;缬沙坦组和螺内酯组的HGFmRNA水平高于SHR对照组 (P <0 0 1 ) ,但低于WKY组 (P均 <0 0 1 ) ,螺内酯组的HGFmRNA水平低于缬沙坦组 (P <0 0 1 )。结论AngⅡAT1

Objective To observe the effect of AT 1 receptor antagonist and mineralocorticoid receptor antagonist on growth factors and type Ⅰ collagen in left ventricle in spontaneously hypertensive rat(SHR) Methods Six week male SHRs( n =18) were randomly to received valsartan (30 mg·kg -1 ·d -1 ), spironolactone (20 mg·kg -1 ·d -1 ) or drinking water Wistar Kyoto rats(WKY)( n =6) were given normal water as control Expression of transforming growth factor β 1 (TGF β 1), hepatocyte growth factor(HGF) and type Ⅰ collagen gene mRNA in heart were determined by RT PCR Results Compared with those of untreated SHR group, cardiac levels of TGF β 1 and type Ⅰ collagen gene mRNA expression in valsartan and spironolactone groups were significantly reduced( P <0 01, respectively) at 13 wks, but remained higher than those in WKY group( P <0 01); cardiac levels of HGF mRNA expression in untreated SHR group were lower than those of WKY group( P <0 01) Compared with those of untreated SHR group, cardiac levels of HGF mRNA expression treated with valsartan and spironolactone were significantly increased( P <0 01, respectively), while still lower than those in WKY group Conclusion These results indicated that AngⅡ AT 1 receptor antagonist and mineralocorticoid receptor antagonist prevented myocardial fibrosis and left ventricular hypertrophy