We studied the effects of spiperone, a selective blocker of dopamine D2 receptors, on the model of pulmonary emphysema provoked by administration of elastase and D-galactosamine hydrochloride to female C57BL/6 mice and characterized by activation of proteases in the lungs and systemic deficiency of its inhibitor α1-antitrypsin. In this model, spiperone prevented the development of inflammatory reaction and reduced the area of emphysematous expanded alveolar tissue. The expression of angiogenic marker CD31 in the lungs increased under these conditions. Regeneration of the damaged microvascular bed under the action of spiperone resulted from recruiting of Notch1+ endothelial progenitor cells (CD45—CD31+CD34+) into the lungs and blockade of the inhibitory effect of dopamine on phosphorylation of VEGF-2 receptors in endothelial cells of different maturity. In addition, spiperone produced a protective effect on hepatocytes and restored the production and secretion of α1-antitrypsin by these cells.

中文翻译：

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阻断多巴胺 D2 受体作为一种新方法刺激 Notch1+ 内皮祖细胞和 C57BL/6 小鼠肺气肿由蛋白酶和 α1-抗胰蛋白酶缺乏症引起的血管生成

我们研究了螺环哌啶酮（一种选择性多巴胺 D2 受体阻滞剂）对雌性 C57BL/6 小鼠施用弹性蛋白酶和 D-半乳糖胺盐酸盐诱发的肺气肿模型的影响，其特征是肺中蛋白酶的激活和全身缺乏其抑制剂α1-抗胰蛋白酶。在这个模型中，spiperone 阻止了炎症反应的发展并减少了肺气肿扩张的肺泡组织的面积。在这些条件下，肺中血管生成标志物 CD31 的表达增加。螺环酮作用下受损微血管床的再生是由于Notch1+内皮祖细胞(CD45-CD31+CD34+)募集到肺中，阻断了多巴胺对不同成熟度内皮细胞VEGF-2受体磷酸化的抑制作用. 此外，螺环酮对肝细胞产生保护作用，恢复这些细胞产生和分泌α1-抗胰蛋白酶。