Crucial role of group IIA phospholipase A2 in pancreatitis-associated adrenal injury in acute necrotizing pancreatitis

Abstract

This study investigated the mechanistic role of group IIA phospholipase A2 (sPLA2-IIA) in the process of pancreatitis-associated adrenal injury in acute necrotizing pancreatitis. One hundred and sixty male Wistar rats were subdivided into a sham-operated group, a sodium taurocholate-induced pancreatitis group, and a pancreatitis group pretreated with sPLA2 inhibitor (pku-mdl-101). The sPLA2 inhibitor was administered by intravenous injection 30 min before induction of pancreatitis. The severity of pancreatitis was evaluated by serum amylase and pancreatic histological score. The serum corticosterone level was measured. Adrenal injury was evaluated by histological evaluation, as well as by sPLA2 activity and sPLA2-IIA protein analysis. Pancreatitis resulted in a time-related increase in serum amylase and in the pancreatic histological score. At first, serum corticosterone increased after 3 h and decreased rapidly after 6 h in pancreatitis. Adrenal injury aggravated during the observation period. The sPLA2 activity in the serum and adrenal glands, as well as the expression of sPLA2-IIA protein in adrenal glands increased and peaked 6 h after the induction of pancreatitis. Pretreatment of sPLA2 inhibitor significantly reduced the severity of pancreatitis and adrenal histological injury, improved the 24-h serum corticosterone levels, and effectively inhibited sPLA2 activity and sPLA2-IIA expression in adrenal glands. The sPLA2 inhibitor attenuated the severity of pancreatitis and pancreatitis-associated adrenal injury. The observations indicate that sPLA2-IIA plays a crucial role in pancreatitis-associated adrenal injury in acute necrotizing pancreatitis.