Jeong E K, Jang H J, Kim S S, Lee S Y, Oh M Y, Kim H J, Eom D W, Ham J Y, Han D J
Department of Anesthesia and Pain Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
Transplant Proc. 2016 May;48(4):1251-7. doi: 10.1016/j.transproceed.2016.01.028.
Polydeoxyribonucleotide (PDRN) is an A2A receptor agonist that induces vascular endothelial growth factor (VEGF) production during the pathological condition of low tissue perfusion. Ischemia-reperfusion injury (IRI) is a major problem after renal transplantation. In the present study, we investigated whether PDRN exhibits reno-protective effects against ischemia-reperfusion-induced acute kidney injury in mice.
Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes, followed by reperfusion for 48 hours. PDRN (8 mg/kg body weight intraperitoneally) was administered 30 minutes before IRI.
Treatment with PDRN significantly decreased neutrophil gelatinase-associated lipocalin levels in the urine, blood urea nitrogen level, and serum creatinine levels as well as kidney tubular injury. Western blotting showed that PDRN significantly increased the levels of vascular endothelial growth factor and B-cell lymphoma protein and attenuated p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, inducible nitric oxide synthase, and Bcl-2-associated X protein levels 48 hours after IRI.
Our findings suggest that PDRN is a potential therapeutic agent for acute ischemia-induced renal damage.
聚脱氧核糖核苷酸(PDRN)是一种A2A受体激动剂,在组织灌注不足的病理状态下可诱导血管内皮生长因子(VEGF)生成。缺血再灌注损伤(IRI)是肾移植后的一个主要问题。在本研究中,我们调查了PDRN对小鼠缺血再灌注诱导的急性肾损伤是否具有肾保护作用。
通过双侧肾蒂阻断30分钟诱导雄性C57BL/6小鼠发生肾缺血再灌注损伤,随后再灌注48小时。在IRI前30分钟腹腔注射PDRN(8mg/kg体重)。
PDRN治疗显著降低了尿液中中性粒细胞明胶酶相关脂质运载蛋白水平、血尿素氮水平和血清肌酐水平以及肾小管损伤。蛋白质印迹法显示,IRI后48小时,PDRN显著提高了血管内皮生长因子和B细胞淋巴瘤蛋白水平,并降低了p38丝裂原活化蛋白激酶、c-Jun氨基末端激酶、诱导型一氧化氮合酶和Bcl-2相关X蛋白水平。
我们的研究结果表明,PDRN是急性缺血性肾损伤的一种潜在治疗药物。