Amelioration of lung ischemia‑reperfusion injury by JNK and p38 small interfering RNAs in rat pulmonary microvascular endothelial cells in an ischemia‑reperfusion injury lung transplantation model.

The inhibition of mitogen‑activated protein kinases (MAPKs), including c‑Jun NH2‑terminal protein kinase (JNK), p38 MAPK (p38) and extracellular signal‑regulated protein kinase 1/2 (ERK1/2), have an important effect on lung ischemia‑reperfusion injury (IRI) during lung transplantation (LT). However, the way in which combined MAPK inhibition exerts optimal protective effects on lung IRI remains to be elucidated. Therefore, the present study evaluated the therapeutic efficacy of the inhibition of MAPKs in rat pulmonary microvascular endothelial cells (PMVECs) in an IRI model of LT. The rat PMVECs were transfected with small interfering RNAs (siRNAs) against JNK, p38 or ERK1/2. Cotransfection was performed with siRNAs against JNK and p38 in the J+p group, JNK and ERK1/2 in the J+E group, p38 and ERK1/2 in the p+E group, or all three in the J+p+E group. Non‑targeting (NT) siRNA was used as a control. The PMVECs were then treated to induce IRI, and the levels of inflammation, apoptosis and oxidative stress were detected. Differences between compared groups were determined using Tukey's honest significant difference test. In all groups, silencing of the MAPKs was shown to attenuate inflammation, apoptosis and oxidative stress to differing extents, compared with the NT group. The J+p and J+p+E groups showed lower levels of interleukin (IL)‑1β, IL‑6 and malondialdehyde, a lower percentage of early‑apoptotic cells, and higher superoxide dismutase (SOD) activity, compared with the other groups. No significant differences were observed in the inflammatory response, SOD activity or early apoptosis between the J+p and J+p+E groups. These findings suggested that the dual inhibition of JNK and p38 led to maximal amelioration of lung IRI in the PMVECs of the IRI model of LT, which occurred through anti‑inflammatory, anti‑oxidative and anti‑apoptotic mechanisms.