MIF抑制剂ISO-1在妊娠大鼠重症急性胰腺炎肺损伤中的作用

目的 探讨巨噬细胞移动抑制因子(MIF)在孕鼠重症急性胰腺炎(SAP)肺损伤中的作用.方法 30只晚期SD孕鼠使用随机数字表法随机分为孕鼠组(SO组)、孕鼠SAP组(SAP组)和孕鼠MIF抑制剂ISO-1预处理组(ISO-1组),每组均为10只.逆行胆胰管注射5%牛磺胆酸钠制备SAP模型.术后12 h处死大鼠取血检测血清淀粉酶(AMY).取胰腺组织及肺组织行病理学检查并评分,免疫组化检测肺组织中MIF、核因子κB(NF-κB)及肿瘤坏死因子α(TNF-α)表达.结果 SAP组孕鼠的血清淀粉酶(AMY)、胰腺及肺组织病理评分较SO组均有显著增高,差异有统计学意义(P<0.05);SAP组孕鼠肺组织中的MIF、NF-κB及TNF-α表达较SO组也显著增强,差异有统计学意义(P<0.05).ISO-1组上述指标较SAP组均有显著改善,差异有统计学意义(P<0.05).MIF的表达与NF-κB及TNF-α的表达均呈正相关,相关系数分别为r=0.815和r=0.787,P<0.05.结论 MIF抑制剂ISO-1对孕鼠急性重症胰腺炎肺损伤具有一定的保护作用,其部分机制可能与抑制NF-κB及TNF-α的激活有关.

Effects of MIF inhibitor ISO-1 on lung injury in rat models of acute pancreatitis in pregnancy

Objective To explore the effects of ISO-1 (macrophage migration inhibitory factor, MIF) on lung injury in pregnant rats with severe acute pancreatitis (SAP). Methods Thirty pregnant SD rats were randomly divided into the sham operation (SO) group, SAP group, and ISO-1 group, with 10 rats in each group. SAP model was estab-lished by retrograde injection of 5%sodium taurocholate into the biliopancreatic duct. The level of serum amylase and histopathological scores of pancreatic and lung tissues were determined. MIF, NF-κB and TNF-α activity in the lung was examined by immunohistochemical methods. Results Serum level of amylase (AMY), histopathological scores of pancreatic and lung tissues and activities of MIF, NF-κB, TNF-αin SAP group increased significantly as compared with those in SO group (P<0.05), and the microscopic lung injuries were gradually aggravated with disease progression (P<0.05). In ISO-1 group, all the above mentioned indexes were reduced significantly in comparison with those in the SAP group (P<0.05). Intrapulmonary levels of MIF was positively associated with the expression of NF-κB and TNF-α(r=0.815, r=0.787, P<0.05). Conclusion MIF inhibitor ISO-1 protects lung from injury in pregnant rats with SAP. It was suggested that MIF was one of the mechanisms in acute pancreatitis in pregnancy with lung injury and may correlate with the activations of NF-κB and TNF-α.