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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 effect of endothelin-1 (ET-1) receptor antagonist BQ123 on the synthesis of collagen type Ⅰ and Ⅲ in left lung in rats with left-shunt right pulmonary hypertension and to explore the mechanism of left-right shunt pulmonary hypertension. Methods: Thirty - four Wistar rats were randomly divided into experimental group Ⅰ (n = 15), experimental group Ⅱ (n = 9) and control group (n = 10). In the experimental group, the left to right shunt pulmonary hypertension model was established by cannula connection. The rats in experimental group Ⅱ started to receive BQ123 four weeks after operation, 50 μg / kg each time for three weeks, for 12 weeks. After operation Pulmonary arterial systolic pressure was measured at 16 weeks. Changes of ET-1 content in rat lung tissue by radioimmunoassay. The effect of BQ123 on the expression of type Ⅰ procollagen and type Ⅲ procollagen in rat lung tissue was detected by RT-PCR. Immunohistochemistry was used to detect the expression of collagen type Ⅰ and type Ⅲ collagen and the relative content of BQ123 in rat lung. Results: The pulmonary arterial systolic pressure and the content of ET-1 in lung tissue were increased in left-to-right shunt rats. The expression of type Ⅰ procollagen and type Ⅲ procollagen mRNA in lung tissue were increased and the relative content of collagen increased. After administration of BQ123, the pulmonary arterial pressure and lung tissue The content of ET-1 decreased, while the expression of type Ⅰ and Ⅲ procollagen mR-NA and the relative content of collagen decreased. CONCLUSION: BQ123 can decrease the content of ET-1 in the lung tissue, inhibit the synthesis of collagen, and the increase of ET-1 and collagen synthesis are involved in the formation of pulmonary hypertension.