Penehyclidine hydrochloride exerts protective effects in rats with acute lung injury via the Fas/FasL signaling pathway
Penehyclidine hydrochloride exerts protective effects in rats with acute lung injury via the Fas/FasL signaling pathway
复制标题
盐酸戊乙奎醚通过Fas/FasL信号通路对急性肺损伤大鼠发挥保护作用
DOI：
10.3892/etm.2019.7340
复制
发表时间：
2019-05-01
影响因子：
2.7
通讯作者：
Song, Xuemin
中科院分区：
文献类型：
--
作者：
Kong, Qian;Wu, Xiaojing;Song, Xuemin
急性肺损伤（ALI）是一种与高发病率和死亡率相关的危重综合征。Fas/Fas配体（FasL）信号通路的激活可能是ALI发展过程中一个重要的病理生理机制。盐酸戊乙奎醚（PHC）显示出抗细胞凋亡的特性，并可能减轻观察到的全身炎症反应。本研究旨在阐明PHC调控ALI大鼠Fas/FasL信号通路的分子机制。采用钝性胸外伤和失血性休克（T/HS）模型，在T/HS前后分别给予PHC治疗。在T/HS后6 h，采集血样和肺组织。采用Western blotting、动脉血气分析、ELISA、苏木精和伊红染色、末端脱氧核苷酸转移酶介导dUTP镍端标记染色、生化指标分析等方法检测肺损伤程度及肺损伤相关的关键信号通路。结果表明，T/HS后给予PHC可通过改善肺氧合，减轻组织病理损伤，降低多形核中性粒细胞计数，降低Fas、FasL、caspase-8、caspase-3、肿瘤坏死因子-α、白细胞介素(IL)-6和IL-1β的表达，有效减轻肺损伤。结果表明，PHC对T/HS诱导的ALI大鼠具有抗凋亡功能并发挥保护作用，其机制可能与抑制Fas/FasL信号通路有关。
Acute lung injury (ALI) is a critical syndrome that is associated with high morbidity and mortality rates. The activation of the Fas/Fas ligand (FasL) signaling pathway may be an important pathophysiological mechanism during ALI development. Penehyclidine hydrochloride (PHC) has been revealed to exhibit anti-apoptotic properties and may attenuate the observed systemic inflammatory response. The present study was performed to elucidate the molecular mechanism of PHC in the regulation of the Fas/FasL signaling pathway in rats with ALI. An ALI rat model was constructed by inducing blunt chest trauma and hemorrhagic shock (T/HS), with PHC administration prior to or following T/HS. At 6 h following T/HS, blood samples and lung tissues were collected. Western blotting, arterial blood gas analysis, ELISA, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and biochemical indicator analysis were performed to determine the degree of lung injury and the key signaling pathways associated with lung damage. The results indicated that the administration of PHC following T/HS effectively attenuates lung injury by improving pulmonary oxygenation, decreasing histopathological damage, decreasing polymorphonuclear neutrophil count and decreasing Fas, FasL, caspase-8, caspase-3, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β expression. The results indicated that PHC exhibits anti-apoptotic functions and exerts protective effects in ALI rats induced by T/HS, which may be attributed to the inhibition of the Fas/FasL signaling pathway.