Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress Syndrome Induced by Oleic Acid in Rats
Xiujuan Yan, Yingxiu Li, Yun Ho Choi, Chongyang Wang, Yihua Piao, Jing Ye, Jingzhi Jiang, Liangchang Li, Huixian Xu, Qingsong Cui, Guanghai Yan, Minggen Jin
Intensive Care Unit, Yanbian University Hospital, Yanji, Jilin, China (mainland)
Med Sci Monit 2018; 24:7186-7198
This study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats.
MATERIAL AND METHODS: Sprague-Dawley rats were randomly divided into control, OA model, and OA + Alprostadil (2.5, 5, and 10 μg/kg, respectively) groups. The ARDS model was induced by femoral vein injection of OA, and alprostadil was administrated immediately. Lung injury was evaluated by lung wet-dry weight ratio (W/D) and histological analyses. Expressions of ACE, inflammatory mediators, apoptotic-related proteins, and proteins in the MAPKs and NF-κB signaling pathways were determined by Western blot or immunohistochemical staining.
RESULTS: Compared with the control group, the OA model group had significantly increased W/D, lung injury score, and collagen deposition at 3 h after OA injection. However, alprostadil (10 μg/kg) treatment significantly reduced OA-induced elevation of these indicators. Additionally, OA-induced expression of TNF-α and IL-1β were suppressed by alprostadil. The OA-induced activation of nuclear factor (NF) κB p65 was also reduced by alprostadil. Furthermore, we found that Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and p38 MAPKs. Alprostadil inhibited Bax but increased Bcl-2, indicating a suppressive role in apoptosis. Remarkably increased expression of ACE in the OA model group was observed, which was decreased by alprostadil.
CONCLUSIONS: Alprostadil has a protective effect on ARDS induced by OA in rats, possibly through inhibiting apoptosis, suppressing the activation of MAPKs and NF-κB signaling pathways, and decreasing ACE protein expression. Therefore, the use of alprostadil in clinical ARDS treatment is promising.
Keywords: Alprostadil, Oleic Acid, Respiratory Distress Syndrome, Adult