Pallio Giovanni, Bitto Alessandra, Pizzino Gabriele, Galfo Federica, Irrera Natasha, Squadrito Francesco, Squadrito Giovanni, Pallio Socrate, Anastasi Giuseppe P, Cutroneo Giuseppina, Macrì Antonio, Altavilla Domenica
Department of Clinical and Experimental Medicine, Section of Pharmacology, Medical School, University of Messina Messina, Italy.
Department of Human Pathology, University of Messina Messina, Italy.
Front Pharmacol. 2016 Aug 23;7:273. doi: 10.3389/fphar.2016.00273. eCollection 2016.
Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.
腺苷受体途径的激活已被证明在改善组织重塑和减弱炎症反应方面是有效的。活动性结肠炎的特征是强烈的炎症反应，导致广泛的组织损伤。症状的改善需要控制炎症过程以及修复和重塑受损组织。我们使用雄性Sprague-Dawley大鼠，在两种实验性结肠炎模型中研究了A2A受体激动剂聚脱氧核糖核苷酸（PDRN）恢复组织结构完整性的能力。在第一个模型中，通过在结肠内单次注入25 mg二硝基苯磺酸（DNBS）（溶于0.8 ml 50%乙醇）诱导结肠炎。6小时后，将动物随机分组，每天分别接受PDRN（8 mg/kg，腹腔注射）、PDRN + A2A拮抗剂[3,7-二甲基-1-炔丙基黄嘌呤（DMPX）；10 mg/kg，腹腔注射]或赋形剂（0.8 ml盐溶液）。在第二个模型中，将硫酸葡聚糖钠（DSS）以8%的浓度溶解于饮用水中。对照动物饮用标准饮用水。24小时后，将动物随机分组，如上所述接受PDRN或PDRN + DMPX。在接受DNBS后7天或DSS后5天处死大鼠。在两种实验性结肠炎模型中，PDRN均改善了与疾病相关的临床症状和体重减轻，并促进了受损组织的组织学修复。此外，PDRN降低了炎性细胞因子的表达、髓过氧化物酶活性和丙二醛水平。同时给予A2A拮抗剂DMPX消除了所有这些作用。我们的研究表明，PDRN可能是改善炎症性肠病期间组织修复的一种有前景的治疗方法。
