Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock

被引:15
|
作者
Liu, Si-bo [1 ]
Liu, Jinjie [1 ,2 ]
Liu, Da-wei [3 ]
Wang, Xiao-ting [3 ]
Yang, Rong-li [1 ]
机构
[1] Dalian Municipal Cent Hosp, Surg Intens Care Unit, Dalian 116000, Shahekou Distri, Peoples R China
[2] Dalian Municipal Cent Hosp, VIP Ward 2, Dalian 116000, Shahekou Distri, Peoples R China
[3] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Crit Care Med, Beijing 100021, Peoples R China
关键词
Acute kidney injury; Apoptosis; Endotoxic shock; Hemodynamics; PARP; 3-aminobenzamide; ADP-RIBOSE POLYMERASE; POLY(ADP-RIBOSE) POLYMERASE; CELL APOPTOSIS; BLOOD-FLOW; INJURY; PARP; 3-AMINOBENZAMIDE; SEPSIS;
D O I
10.1159/000435815
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Poly-(ADP-ribose) polymerases (PARPs), a super family of enzymes, play important roles in preserving genomic integrity, regulating transcriptions, protecting telomeres and determining cell fate. PARP overactivation leads to metabolic disorder and cell injury via depletion of energy substance. However, it is still unclear whether PARP overactivation happens during acute kidney injury (AKI) caused by endotoxic shock (ES). Here, we built a canine model of lipopolysaccharide-induced ES to explore the role of PARP during the development AKI. We also used an intravenous injection of 3-amino-benzamide (3-AB) to further explore whether PARP inhibition rescues the kidney from injury. Cell fate and energy metabolism were detected to explore the underlying mechanisms. As a result, Western blot and immunohistochemistry assays showed PARP overactivation in the very early phase of ES. Through PARP inhibition by 3-AB, we observed significant improvement of systemic hemodynamics, renal hemodynamics, renal oxygen metabolism and renal tubular cell apoptosis. These findings indicated that overactivation of PARP plays an important role in septic AKI. Inhibition of PARP overactivation may protect renal function against hemodynamic disorder, renal metabolism disturbance and renal cell apoptosis during endotoxic AKI. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:281 / 292
页数:12
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