促红细胞生成素预处理对重症急性胰腺炎促炎抗炎失衡的影响

摘要

Objective To evaluate the effect of pretreatment with erythropoietin (EPO) on disordered pro- and anti-inflammatory balance in rats with severe acute pancreatitis (SAP) and explore the underlying mechanisms. Methods Ninety healthy male SD rats were randomized equally into sham-operated group, SAP group and EPO pretreatment group. SAP model was induced in the latter two groups by retrograde injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before SAP, and normal saline was administered in the other two groups. Serum amylase activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time points after the operation. The translocation and activation of nuclear factor-KB (NF-kB) in the pancreatic tissue was detected using immunofluorescence staining, and pancreatic pathologies were evaluated. Results Compared with SAP group, EPO group showed a markedly decreased activation rate of NF-kB after SAP except for 12 h (P＜0.05), significantly decreased serum amylase activity at 3, 6, and 12 h (P＜0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P＜0.05), whereas serum IL-10 underwent no significant changes. The rats in EPO group showed an obviously milder pancreatic pathology than those in SAP group at 6, 12, and 24 h (P＜0.05). Conclusion EPO can effectively inhibit NF-kB activation by regulating the inflammatory mediators and restoring the pro-and anti-inflammatory balance to alleviate SAP in rats.%目的 评估促红细胞生成素(EPO)预处理对重症急性胰腺炎促炎抗炎失衡的干预效果及探讨其可能机制.方法 健康雄性SD大鼠随机分成3组:假手术(SO)组、重症急性胰腺炎(SAP)组和EPO预处理组,每组各30只.SAP组和EPO组建立逆行胆胰管注射3.5％牛黄胆酸钠法(1 ml/kg) SAP模型,EPO组建模前1h予静脉注射促红细胞生成素(3000 U/kg,1000 U/ml),而SO组和SAP组予静脉注射等体积生理盐水.术后第1、3、6、12、24小时取血清和胰腺标本.检测血清淀粉酶活性；ELISA法检测血清IL-18水平,放射免疫法检测血清IL-10水平.免疫荧光法检测胰腺组织核因子-kappaB转运激活情况；胰腺组织石蜡切片HE染色,进行胰腺病理学评分.结果 与SAP组相应时点比较,EPO组核因子-kappaB激活率(除12h外)显著降低(P＜0.05)；血清淀粉酶活性显著降低,3、6、12 h(P＜0.05)；血清IL-18水平显著降低,3、6、24 h(P＜0.05),血清L-I0水平无明显降低；病理总评分降低,6、12、24 h(P＜0.05).结论 EPO预处理可通过抑制核因子-kappaB激活,减少促炎细胞因子产生,而对抗炎细胞因子影响不明显,进而调控促炎-抗炎失衡状态,改善SAP病情.