Author:
Wang Yuting,Qiu Li,Yu Delong,Yu Yijun,Hu Liqun,Gu Ye
Abstract
Abstract
Background
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.
Methods
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 α1 receptor, α2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively.
Results
In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α1, α2 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 α1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α1 and α2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca2+ 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.
Conclusion
In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α1 and α2 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 α1 and α2 receptor and their downstream signaling pathways.
Funder
National Outstanding Youth Science Fund Project of National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC