Poly(ADP-ribose) polymerase inhibition suppresses inflammation and promotes recovery from adrenal injury in a rat model of acute necrotizing pancreatitis

BMC Gastroenterology

Research Article

Peng Ma¹  Liang Zhao¹  Kailiang Zhao¹  Qiao Shi²  Jia Yu²  Weixing Wang²  Wenhong Deng²  Teng Zuo²  Chen Chen² 

[1] Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, People’s Republic of China;Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, People’s Republic of China;Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, People’s Republic of China;

关键词: Acute necrotizing pancreatitis;    Poly(ADP-ribose) polymerase;    3-Aminobenzamide;    Adrenal insufficiency;    Adrenal injury;    Apoptosis;   

DOI  :  10.1186/s12876-016-0493-5

 received in 2015-10-26, accepted in 2016-07-14,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPoly(ADP-ribose) polymerase (PARP) participates in multi-organ failure in various inflammatory diseases including acute necrotizing pancreatitis (ANP). Since pancreatitis-associated adrenal insufficiency is partly caused by inflammatory damage to the adrenal cortex, we examined whether PARP antagonism could alleviate adrenal insufficiency in a rat model of ANP.MethodsANP was induced by retrograde infusion of sodium taurocholate into the bile-pancreatic duct. At 30 min prior to taurocholate infusion, rats were pretreated with the PARP inhibitor 3-Aminobenzamide (3-AB, 20 mg/kg) or vehicle. Pancreatic pathological injury, adrenal histology, neutrophil infiltration, cell apoptosis, and serum corticosterone level were assessed at various times points. Activities of poly(ADP-ribosyl)ated protein (PAR), nuclear factor-kappaB (NF-kB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in the adrenal were also examined.ResultsPARP overactivation in ANP rats is associated with reduced serum corticosterone level and marked cellular alterations in adrenocortical tissue. Inflammatory stress caused by ANP reduced adrenal corticosterone release. 3-AB reduced the activation of PARP and inflammatory markers, decreased myeloperoxidase activity, attenuated adrenal morphologic lesions and cells apoptosis, simultaneously improved the impaired adrenal function.ConclusionsOur data demonstrate the involvement of PARP overactivation in the pathogenesis of adrenal dysfunction after ANP. PARP inhibition may suppress inflammation and promote functional recovery from adrenal injury.

【 授权许可】

CC BY   
© The Author(s). 2016