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| 抑制PAI-1对大鼠左心疾病所致肺高压的影响 |
| Effect of PAI-1 inhibition on pulmonary hypertension caused by left heart disease in rats |
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| DOI：10.12089/jca.2020.09.015 |
| 中文关键词: 纤溶酶原激活物抑制剂1 左心疾病 肺高压 IMD-1622 大鼠 |
| 英文关键词: PAI-1 Left heart disease Pulmonary hypertension IMD-1622 Rats |
| 基金项目: |
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| 中文摘要: |
目的 探讨纤溶酶原激活物抑制剂1（PAI-1）的抑制剂IMD-1622用于治疗左心疾病所致肺高压（PH-LHD）大鼠的效果。
方法 SD1月长鼠40只，采用随机数字表法均分为四组：对照组（C组）、假手术组（S组）、模型组（M组）和抑制剂组（I组），每组10只。C组，不做任何处理；S组，麻醉后吸氧，经左侧2～3肋间侧开胸，然后关胸；M组，制作PH-LHD模型；I组，PH-LHD模型建模成功后腹腔注射IMD-1622 20mg/kg。 四组大鼠给予正常实验室饮食和水喂养至8周后，监测CVP、MAP、平均肺动脉压（MPA）、左心房压（LAP），计算肺血管阻力（PVR）和体循环阻力（SVR）；取肺组织切片测量肺动脉中膜层厚度；HE染色免疫组化检测PAI-1含量；免疫荧光法检测肺组织中内皮素1（ET-1）及血栓素A2（TXA2）含量。
结果 M组和 I组MPA、LAP、PVR明显高于C组和S组，M组明显高于I组(P<0.05)。M组和I组肺动脉中膜层厚度明显厚于C组和S组，M组明显厚于I组（P<0.05）。M组和I组肺组织PAI-1含量组化灰度分析数值均明显高于C组和S组，M组明显高于I组（P<0.05）。M组和I组肺组织中ET-1和TXA2荧光表达明显强于C组和S组，M组明显强于I组（P<0.05）。
结论 PAI-1抑制剂IMD-1622可以减轻肺动脉中膜层增厚，改善左心疾病所致肺高压。 |
| 英文摘要: |
Objective To investigate the effect of PAI-1 inhibitor IMD-1622 in the treatment of PH-LHD rats caused by left heart disease.
Methods Forty young SD rats were randomly divided into 4 groups (n = 10): control group (group C), sham group (group S), model group (group M) and inhibitor group (group I). Rats in group C received no treatment. Oxygen inhalation after anesthesia, thoracotomy through the left 2 to 3 intercostal sides and then sternal closure in group S. PH-LHO model was established in group M. Rats in group I were treated with IMD-1622 (20 mg/kg) intraperitoneally after successful modeling. Four groups of rats were given normal laboratory diet and water for 8 weeks, and central venous pressure (CVP), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPA), left atrial pressure (LAP) were monitored, and calculated PVR and SVR. Pulmonary tissue section to measure the thickness of the middle layer of the pulmonary artery, PAI-1 expression was detected by immunohistochemical staining of HE, the expression of endothelin 1 (ET-1) and thromboxane A2 (TXA2) in lung tissues were determined by immunofluorescence.
Results The MPA, LAP, PVR in group M and I were significantly higher than those in groups C and S, where as group M was significantly higher than that in group I (P < 0.05). Middle layer of pulmonary artery in group M and I were significantly thicker than group C and S, and group M was thicker than group I (P < 0.05). PAI-1 expression of group M and I were higher than group C and S, while group M was significantly higher than group I (P < 0.05). Expression of ET-1 and TXA2 in lung tissue of group M and I were higher than group C and S, and group M was significantly higher than that of group I (P < 0.05).
Conclusion PAI-1 inhibitor IMD-1622 can reduce the thickness of the middle layer of pulmonary artery, so that improve the pulmonary hypertension caused by left heart disease. |
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