Zhou Hong, Jiang Chunhui, Gu Lei, Liu Y E, Sun Longci, Xu Qing
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Biomed Rep. 2016 Jun;4(6):667-672. doi: 10.3892/br.2016.645. Epub 2016 Apr 4.
The aim of the present study was to explore the influence of melatonin (MT) on rats with liver ischemia reperfusion injury (IRI) and its mechanism. A total of 66 male Sprague-Dawley rats were randomly divided into 3 groups: i) Normal control group, ii) ischemia reperfusion group (IR group) and iii) melatonin treatment group (MT group). Rats in the MT group were administered an intraperitoneal injection of MT (10 mg/kg, 1 ml) at 70 and 35 min before ischemia, early reperfusion, and 1 and 2 h after reperfusion, respectively. Blood was removed at the normal time-point (prior to any processes), 35 min before ischemia, 2, 4, 8 and 24 h after reperfusion. Subsequently the rats were sacrificed. The pathological changes of liver tissues, interleukin-1 receptor antagonist (IL-1Ra) gene and IL-1 expression levels were detected. There were no evident differences between the immediate reperfusion and 2 h IR group and MT group. The liver structure injury of the 4, 8 and 24 h MT groups were improved to various differences compared to the corresponding IR group; liver IL-1β of the MT group at 35 min after ischemia, and 2, 4, 8 and 24 h after reperfusion was evidently lower than that of the IR group (P<0.05); IL-1Ra mRNA expression in the 2 h MT group was higher compared to the 2 h IR group by 4.85-fold; and IL-1Ra mRNA expression in the 4 h MT group was higher compared to the 4 h IR group by 9.34-fold. Differences between two groups at other time-points were <2-fold. In conclusion, MT can upregulate IL-1Ra gene expression by reducing generation of IL-1 thus reducing IRI.
本研究旨在探讨褪黑素(MT)对肝缺血再灌注损伤(IRI)大鼠的影响及其机制。将66只雄性Sprague-Dawley大鼠随机分为3组:i)正常对照组,ii)缺血再灌注组(IR组)和iii)褪黑素治疗组(MT组)。MT组大鼠在缺血前70分钟和35分钟、再灌注早期以及再灌注后1小时和2小时分别腹腔注射MT(10mg/kg,1ml)。在正常时间点(任何操作之前)、缺血前35分钟、再灌注后2、4、8和24小时取血。随后处死大鼠。检测肝组织的病理变化、白细胞介素-1受体拮抗剂(IL-1Ra)基因和IL-1表达水平。即刻再灌注组与2小时IR组和MT组之间无明显差异。与相应的IR组相比,MT组4、8和24小时的肝结构损伤有不同程度的改善;MT组在缺血后35分钟以及再灌注后2、4、8和24小时的肝IL-1β明显低于IR组(P<0.05);MT组2小时的IL-1Ra mRNA表达比2小时IR组高4.85倍;MT组4小时的IL-1Ra mRNA表达比4小时IR组高9.34倍。其他时间点两组间差异<2倍。综上所述,MT可通过减少IL-1的生成上调IL-1Ra基因表达,从而减轻IRI。