Role of hippocampal cyclophilin D in sepsis-associated encephalopathy in rats

Abstract

Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats. Methods A total of 36 adult male Sprague-Dawley rats, aged 3-4 months, weighing 300-400 g, were randomly divided into 3 groups (n =12 each) using a random number table: sham operation group (Sham group), sepsis group (S group), and sepsis + CypD inhibitor cyclosporin A group (CsA group). Sepsis was induced by cecal ligation and puncture (CLP). Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test, and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c), CypD, caspase-3, brain-derived neurotrophic factor (BDNF), phosphorylated protein kinase A (p-PKA), and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB). Results Compared with group Sham, the escape latency was significantly prolonged, the space exploration time was shortened, the expression of Cyt c, CypD, caspase-3, p-PKA and p-CREB was up-regulated, and the expression of BDNF was down-regulated in S and CsA groups (P<0.05). Compared with group S, the escape latency was significantly shortened, the space exploration time was prolonged, the expression of Cyt c, CypD, caspase-3, p-PKA and p-CREB was down-regulated, and the expression of BDNF was up-regulated in group CsA (P<0.05). Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy, and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats. Key words: Sepsis; Cyclophilins; Hippocampus; Brain diseases