BQ_(123)对左向右分流肺动脉高压大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响

Influence of BQ_(123) on the synthesis of type Ⅰ,Ⅲ collagen in rats' lungs with left to right shunt pulmonary hypertension

目的:研究内皮素-1(ET-1)受体拮抗剂BQ123对左向右分流肺动脉高压大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响,并探讨左向右分流肺动脉高压的发生机理。方法:选择Wistar大鼠34只,随机分为实验Ⅰ组(n=15),实验Ⅱ组(n=9),对照组(n=10)。实验组大鼠采用套管连接法建立颈部左向右分流肺动脉高压模型,实验Ⅱ组大鼠术后4周开始给予BQ123,每次50μg/kg,每周3次,连用12周,术后16周测取大鼠肺动脉收缩压。放射免疫法测定大鼠肺组织ET-1含量变化。RT-PCR检测BQ123对大鼠肺组织Ⅰ、Ⅲ型前胶原mRNA表达的影响。免疫组化法检测BQ123对大鼠肺组织Ⅰ、Ⅲ型胶原表达及相对含量的影响。结果:左向右分流大鼠肺动脉收缩压及肺组织ET-1含量升高,肺组织Ⅰ、Ⅲ型前胶原mRNA的表达增强,胶原蛋白相对含量增加;应用BQ123后大鼠肺动脉压力及肺组织ET-1含量降低,Ⅰ、Ⅲ型前胶原mR- NA的表达及胶原相对含量降低。结论:BQ123可降低肺组织ET-1含量,抑制胶原合成,ET-1和胶原合成增加均参与了肺动脉高压的形成过程。

Objective: To investigate the pathogenesis of pulmonary hypertension due to left to right shunt, and study the influence of BQ123, the endothelin-1 receptor antagonist, on the synthesis of type Ⅰ, Ⅲ pulmonary collagen in rats' lungs with left to right shunt pulmonary hypertension. Methods: Thirty-four male Wistar rats were divided into experiment Ⅰ group (n=15), experiment Ⅱ group (n=9), and control group (n=10). Rats in experiment Ⅰ ,Ⅱ group were made cervical left to right shunt pulmonary hypertension model by cuff technique; additionally, 4 weeks later, rats in experiment Ⅱ group were treated with BQ123 by 50μg/kg, 3 times per week for 12 weeks; they were determined the pulmonary artery pressure 16 weeks later, measured lung ET-1 concentrations by radioimmunoassay, measured the influence of BQ123 on the synthesis of type Ⅰ,Ⅲ procollagen and their collagen contents in rats' lungs with left to right shunt by RT-PCR or immunohistochemistry staining respectively. Results: The pulmonary artery pressures and ET-1 concentrations were significantly elevated in experiment Ⅰ group compared with experiment Ⅱ and control group (P<0.05, P<0.001 respectively). The expression level of mRNA of type Ⅰ ,Ⅲ procollagen was significantly elevated in experiment Ⅰ group in contrast with experiment Ⅱ and control group (P<0.05, P<0.001); it was distinctly different between experiment Ⅱ and control group (P<0.05). Immunohistochemistry staining analysis showed that the type Ⅰ ,Ⅲ collagen contents were distinctly raised in experiment Ⅰ group compared with experiment Ⅱ and control group (P<0.05, P<0.001), and it was significantly different between experiment Ⅱ and control group (P<0.05). Conclusion: ET-1 and collagen synthesis both participate the development of pulmonary hypertension. BQ123 can decrease the ET-1 concentrations in lung tissue and inhibit pulmonary collagen synthesis.