Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress Syndrome Induced by Oleic Acid in Rats

Yan, Xiujuan; Li, Yingxiu; Choi, Yun Ho; Wang, Chongyang; Piao, Yihua; Ye, Jing; Jiang, Jingzhi; Li, Liangchang; Xu, Huixian; Cui, Qingsong; Yan, Guanghai; Jin, Minggen

The lung W/D ratio, cytokine levels, and H&E and Masson trichrome staining of lung tissues were evaluated. The W/D ratio is considered as an indicator of lung edema [44] , and OA has been reported to be able to augment edema formation and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice [45] . TNF-a is known as a pro-inflammatory cytokine and can stimulate the production of other cytokines [46, 47] . Its production has been reported to be significantly increased in ALI/ARDS patients [48, 49] . Masson trichrome staining was performed to observe the collagen formation in bronchial airways. Our results showed typical pathological changes in the lungs of OA-administrated rats, such as marked alveolar fluid, thickening of the alveolar wall and lungs, alveolar wall disruption and leukocyte infiltration, and collagen deposition in the lungs. The expression of TNF-a and IL-1b in the lung tissues were significantly increased, and the W/D ratio was increased in ARDS rats. The OA + Alprostadil group showed clearly reduced lung damage, the W/D ratio of rat lung tissues, and the production of TNF-a and IL-1b, as well as collagen formation, as compared with the OA model group. These data indicate the protective role of alprostadil in ARDS. NF-kB is implicated in the regulation of inflammatory and immune responses, which play an important role in the development of ARDS. MAPKs also have critical roles in the regulation of cell growth, differentiation, and control of cellular responses to cytokines and stress [50] . NF-kB and MAPKs signaling pathways can be activated by OA to regulate the release of proinflammatory cytokines, such as TNF-a and IL-1b [51]. More recent studies have suggested that alprostadil reduced LPSinduced ALI through down-regulating NF-kB activity and inhibiting expression of harmful inflammatory cytokines [52] . Our results showed that OA administration markedly increased the phosphorylation of NF-kB p65 and MAPKs, including p38 MAPK, ERK1/2, and JNK. However, alprostadil can completely reverse the increased activation of MAPKs and NF-kB signaling pathways induced by OA. Thus, we demonstrated that Alprostadil can protect against OA-induced ARDS through inhibiting the MAPKs and NF-kB signaling pathways.