血管紧张素受体与心肌胶原代谢关系的研究

Role of Angiotensin Ⅱ Receptors(ATRs) in Metabolism of Myocardial Collagen

目的 研究血管紧张素Ⅱ受体在心肌胶原代谢中的作用。方法 应用放射免疫结合分析、生化测定、病理检查结合计算机分析等方法检测大鼠腹主动脉缩窄后 10周 ,左室心肌胶原形态、胶原溶积分数 (CVF)、血管周围胶原面积 (PVCA)、胶原浓度 (HC)、Ⅰ、Ⅲ型胶原比值 (Ⅰ /Ⅲ )以及血管紧张素Ⅱ含量 (AngⅡ )和血管紧张素Ⅱ受体的最大结合量 (Bmax)。结果 手术组左室心肌CVF、PVCA、HC、Ⅰ /Ⅲ、AngⅡ和Bmax均显著高于假手术对照组 (P <0 0 5 ,P<0 0 1) ,心肌胶原异常堆积。AngⅡ含量与心肌胶原浓度 (HC)呈显著正相关 (r1=0 90 45 ,P <0 0 1)。Irbesartan治疗后 ,上述参数可显著降低 (P <0 0 5 ,P <0 0 1) ,异常堆积的胶原消失。CGP42 112A可明显降低血管紧张素Ⅱ受体的Bmax(P <0 0 1) ,而CVF、PVCA、HC、Ⅰ /Ⅲ、AngⅡ与手术组无显著差异 (P >0 0 5 )。 结论 压力超负荷时 ,大鼠心肌胶原增生 ,间质网络发生重建 ,心脏局部产生的AngⅡ参与了这一病理生理过程 ,并主要通过血管紧张素Ⅱ的 1型受体 (ATR1)来发挥作用。

Objective\ To investigate the role of angiotensin Ⅱ receptors in metabolism of myocardial collagen. Methods\ The collagen volume fraction(CVF), perivascular circumferential area(PVCA), hydroproline concentration(HC), ratio of collagen type Ⅰto type Ⅲ(Ⅰ/Ⅲ),angiotensin Ⅱ(AngⅡ) content and the maximal binding capacity (Bmax) of ATRs were studied. The methods of radioimmunoassay(RIA),biochemistry assay, and pathological examination were used. Results\ Ventricular myocardial CVF, PVCA, HC, Ⅰ/Ⅲ, AngⅡ and Bmax of ATRs in WKY rats were significantly higher than those in sham operation(SO)( P <0 05 or P <0 01),suggesting the collagen was abnormally accumulated in rats heart muscles. AngⅡ was positivily correlated with HC(r\-1=0 9045, P <0 01). After treament of Irbesartan, All above parameter were reduced significantly( P <0 05 or P <0 01), abnormally accumulated collagen was disappeared. While after treament of CGP42112A,an ATR 2 antagonist, Bmax of ATRs was markedly decreased( P <0 01), but CVF, PVCA, HC,Ⅰ/Ⅲ, AngⅡ showed little changes( P >0 05). Conclusion\ Obvious hyperplasia of myocardial collagens and remodeling of collagen network occurred after pressure overload. Local produced AngⅡ involves in the process,it's effects is mainly mediated by angiotensin Ⅱ 1 type receptor(ATR\-1)