The involvement of p38MAPK in the rat model of lower-extremity arterial ischemia-reperfusion injury.

Abstract

This study aims to investigate the regulatory role of p38 mitogen-activated protein kinase (p38MAPK) in rats with lower-extremity arterial ischemia-reperfusion injury. A total of 60 Sprague-Dawley (SD) rats were randomly divided into four groups: control group (Group A), lower-extremity arterial ischemia-reperfusion group (Group B), lower-extremity arterial ischemic postconditioning group (Group C), and lower-extremity arterial ischemic postconditioning + SB203580 group (Group D, 5 μmol/L SB203580, the inhibitor of MAPK pathway, was injected after lower-extremity arterial ischemic postconditioning). The lower-extremity arterial vessels were collected after 24 h. The apoptosis in the lower-extremity arterial vessel in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The expression of phosphorylated (p)-p38MAPK was measured via Western blotting, and the level of p-activating transcription factor-2 (ATF-2) was detected via immunohistochemical method. The positive rate of apoptotic cells (%) in Group B was significantly increased compared to that in Group A (p<0.05). However, the positive rate was statistically decreased by postcondition in Group C, the rate was further reduced after injection of SB203580 in Group D compared to Group B (p<0.05). Compared with that in Group C, the expressions of p-p38MAPK and p-ATF-2 in Group D were significantly downregulated after injection of SB203580 (p<0.05). Lower-extremity arterial ischemia-reperfusion postconditioning can significantly reduce the apoptosis level in vascular tissues, decrease the expressions of p-p38MAPK and downstream factor ATF-2, and alleviate the damage in lower-extremity arterial vessels. The inhibition of MAPK pathway further restricted the apoptosis and contributed to a promoting role in the recovery of lower-extremity arterial ischemia-reperfusion injury.