Lorenzi Teresa, Trombettoni Maria Michela Cappelletti, Ghiselli Roberto, Paolinelli Francesca, Gesuita Rosaria, Cirioni Oscar, Provinciali Mauro, Kamysz Wojciech, Kamysz Elzbieta, Piangatelli Cristiano, Castellucci Mario, Guerrieri Mario, Morroni Manrico
Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, School of Medicine, Università Politecnica delle MarcheItaly.
General Surgery and Surgery Methodology Clinic, Università Politecnica delle MarcheOspedali Riuniti, Ancona, Italy.
Am J Transl Res. 2017 Jul 15;9(7):3374-3386. eCollection 2017.
This study investigates the effects of the antimicrobial cationic peptide omiganan-alone and combined with the antibiotic imipenem-on colonic anastomosis healing in presence of intraperitoneal sepsis induced in a rodent model of cecal ligation and puncture (CLP).
Forty male Wistar rats were divided into 5 groups of 8 animals. Group 1 (control group) underwent laparotomy and cecal mobilization and the next day received left colon anastomosis. In group 2 (CLP without treatment), group 3 (CLP + imipenem), group 4 (CLP + omiganan), and group 5 (CLP + omiganan + imipenem), the left colon anastomosis was performed the day after CLP. Imipenem and omiganan were administered by intraperitoneal injection immediately before anastomosis construction and subsequently at 24 h intervals until the 7th postoperative day, when rats were sacrificed. Anastomotic bursting pressure was measured in situ. Tissue samples were collected for determination of hydroxyproline content and histological characteristics.
Only rats receiving omiganan + imipenem displayed re-epithelialization, reduced neovascularization of granulation tissue, and a bursting pressure that was similar to that of controls. Omiganan-alone and combined with imipenem-was associated with a better control of inflammatory parameters than imipenem alone. In addition omiganan, like imipenem, counteracted the collagen depletion typical of sepsis.
This experimental study demonstrates the efficacy of the new antimicrobial agent omiganan, alone and in combination with imipenem, in delaying the effects of intraperitoneal sepsis on colonic anastomosis healing and provides evidence of the value of omiganan as a therapeutic agent.
本研究在盲肠结扎穿刺(CLP)诱导的啮齿动物腹腔脓毒症模型中,调查抗菌阳离子肽奥米加南单独使用以及与抗生素亚胺培南联合使用对结肠吻合口愈合的影响。
40只雄性Wistar大鼠被分为5组,每组8只。第1组(对照组)接受剖腹术和盲肠游离,次日进行左结肠吻合。在第2组(未治疗的CLP组)、第3组(CLP + 亚胺培南组)、第4组(CLP + 奥米加南组)和第5组(CLP + 奥米加南 + 亚胺培南组)中,CLP术后次日进行左结肠吻合。在吻合构建前即刻通过腹腔注射给予亚胺培南和奥米加南,随后每隔24小时给药一次,直至术后第7天处死大鼠。原位测量吻合口破裂压力。收集组织样本以测定羟脯氨酸含量和组织学特征。
只有接受奥米加南 + 亚胺培南的大鼠出现了再上皮化,肉芽组织的新生血管形成减少,并且破裂压力与对照组相似。单独使用奥米加南以及与亚胺培南联合使用,比单独使用亚胺培南能更好地控制炎症参数。此外,奥米加南与亚胺培南一样,抵消了脓毒症典型的胶原蛋白消耗。
本实验研究证明了新型抗菌剂奥米加南单独使用以及与亚胺培南联合使用在延缓腹腔脓毒症对结肠吻合口愈合影响方面的疗效,并提供了奥米加南作为治疗药物价值的证据。