Osman Afaf S, Osman Ahmed H, Kamel Mahmoud M
Department of Medical Pharmacology, Faculty of Medicine Cairo University Giza Egypt.
Department of Pathology, Faculty of Veterinary Medicine Cairo University Giza Egypt.
JGH Open. 2017 Nov 14;1(3):105-111. doi: 10.1002/jgh3.12018. eCollection 2017 Nov.
Hepatic ischemia reperfusion injury is the main cause of liver failure following liver surgery, so an effective method is needed to prevent or reduce this hepatic injury. The aim of the present study is to investigate the potential effect of ischemic preconditioning versus pharmacological preconditioning with lisinopril or verapamil for protection against hepatic ischemia reperfusion injury induced in rats.
Rats were divided into six groups. Group I served as control untreated. Rats of group II were subjected to laparotomy without induction of ischemia reperfusion. Ischemia reperfusion by ligation of the portal trait for 30 min, followed by reperfusion for 2 h, was performed in rats of groups III-VI. Ischemic preconditioning was performed for rats of group IV before induction of ischemia reperfusion. Lisinopril and verapamil was given daily for 3 days before induction of ischemia reperfusion in groups V and VI, respectively. Serum level of liver transaminases and liver malondialdehyde content were measured, and hepatic histopathological examination was assessed.
Induction of ischemia reperfusion resulted in significant elevation of liver transaminases and liver malondialdehyde content associated with significant hepatic histopathological injury that were significantly improved by ischemic preconditioning, lisinopril, or verapamil treatment. Verapamil showed the most significant improvement compared with ischemic preconditioning or lisinopril treatment.
Ischemic preconditioning and pharmacological preconditioning by lisinopril or verapamil can protect against hepatic ischemia reperfusion probably through inhibition of oxidative stress and neutrophil infiltration. The most potent protection is demonstrated by verapamil treatment.
肝缺血再灌注损伤是肝脏手术后肝衰竭的主要原因,因此需要一种有效的方法来预防或减轻这种肝损伤。本研究的目的是探讨缺血预处理与赖诺普利或维拉帕米药物预处理对大鼠肝缺血再灌注损伤的潜在保护作用。
将大鼠分为六组。第一组作为未处理的对照组。第二组大鼠接受剖腹手术但不诱导缺血再灌注。第三至六组大鼠通过结扎门静脉30分钟诱导缺血再灌注,随后再灌注2小时。第四组大鼠在诱导缺血再灌注前进行缺血预处理。第五组和第六组大鼠分别在诱导缺血再灌注前3天每天给予赖诺普利和维拉帕米。检测血清肝转氨酶水平和肝脏丙二醛含量,并进行肝脏组织病理学检查。
诱导缺血再灌注导致肝转氨酶和肝脏丙二醛含量显著升高,伴有明显的肝脏组织病理学损伤,缺血预处理、赖诺普利或维拉帕米治疗可显著改善这些损伤。与缺血预处理或赖诺普利治疗相比,维拉帕米显示出最显著的改善。
缺血预处理以及赖诺普利或维拉帕米的药物预处理可能通过抑制氧化应激和中性粒细胞浸润来保护肝脏免受缺血再灌注损伤。维拉帕米治疗显示出最强的保护作用。