Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, HanZheng Street 473# QiaoKou District, Wuhan, 430033, China.
Eur J Med Res. 2022 Nov 8;27(1):238. doi: 10.1186/s40001-022-00842-5.
To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock.
Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α receptor, α receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively.
In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α, α receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α and α receptor-related signaling pathways in whole lung tissues, and inhibit Ca signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region.
In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α and α receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α and α receptor and their downstream signaling pathways.
观察α肾上腺素能受体抑制剂酚妥拉明（PTL）在伴有休克的兔急性肺栓塞（APE）模型中的作用和机制。
24 只新西兰兔随机分为假手术组（S 组，n=8）、模型组（M 组，n=8）和 PTL 组（n=8），建立 APE 合并休克模型。评估平均肺动脉压（MPAP）、外周平均动脉压（MAP）和肺循环时间。检测和比较肺栓塞（PE）和非肺栓塞（non-PE）区域肺组织中α受体、α受体及其下游分子的表达水平。
在 M 组中，PE 和 non-PE 区域的α受体相关信号通路明显激活，表现为α、α受体和磷脂酶 C（PLC）上调；磷酸化蛋白激酶 A（p-PKA）的表达水平明显下调；肌球蛋白轻链激酶（MLCK）和α-平滑肌肌动蛋白（α-SMA）水平上调。PTL 治疗可明显改善肺及全身循环衰竭：降低 MPAP，恢复 non-PE 区血流，缩短肺循环时间，升高 MAP，恢复循环衰竭。PTL 诱导的α受体及其下游分子 PLC 在 PE 和 non-PE 区域的表达明显下调，α受体的表达也下调，p-PKA 的表达水平明显上调。PTL 治疗可抑制全肺组织的α和α受体相关信号通路，抑制 Ca 信号通路。MLCK 和α-SMA 的表达水平明显下调。与 PE 区域相比，non-PE 区域α受体及其下游分子的表达水平变化更为显著。
在伴有休克的 APE 模型中，全肺交感神经活性增强，α和α受体及其下游信号激活可能介导全肺血流衰竭。PTL 治疗可有效恢复 non-PE 区肺血流，改善肺及全身循环衰竭，可能通过下调α和α受体及其下游信号通路。
