CNI-1493对重症急性胰腺炎大鼠外周血多形核粒细胞功能的影响

The effect of CM 1493 on the function of peripheral polymorphonuclear granulocyte in rats with severe acute pancreatitis.

目的 探讨p38MAPK信号传导通路阻断剂(CNI-1493)对大鼠重症急性胰腺炎(severeacute pancreatitis SAP)时外周血多形核粒细胞(polymorphonuclear,PMN)功能影响。方法 以胰胆管逆行注射5％牛磺胆酸钠建立SD大鼠SAP模型,将54只SD大鼠随机分为3组:假手术组(SO,n=18);SAP组(SAP n=18);CNI-1493治疗组(CNI,n=18),术后3h、6h、12h取血,用密度梯度法分离PMN,用流式细胞仪测定呼吸爆发功能,并测定PMN释放髓过氧化物酶(MPO)的变化情况。结果SAP组PMN呼吸爆发亢进,MPO释放明显增加,在各时间点上CNI-1493都能抑制PMN的功能亢进,减少MPO的释放。结论 CNI-1493可以明显抑制SAP时PMN的病理性功能亢进,是治疗SAP的重要机制之一,提示可能具有临床应用的前景。

Objective To investigate the effect of CNI-1493, a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, on the function of peripheral polymorphonuclear granulocyte in rats with severe acute pancreatitis (SAP). Methods The SAP model was induced by the bili-pancreatic duct infusion with 5% sterile sodium taurocholate solution. 54 SD rats were randomly divided into three groups; sham operation group (SO, n = 18), SAP group (n=18), and CNI group (SAP rats were treated with CNI-1493,n = 18). Blood samples were collected at 3 h, 6 h and 12 h after operation. PMNs were isolated with density gradient centrifugation, and respiratory burst of PMNs was determined by using flow cytometry. The level of MPO released by PMN was also determined. Results The respiratory burst function of PMN in rats with SAP was excessive and the amount of MPO released by PMN was greatly increased. CNI-1493 inhibited the excessive function of PMN and reduced the level of MPO released by PMN. Conclusions One of the important mechanisms of CNI-1493 in treating SAP is that it can restrain the pathologic hyperfunction of PMN, suggesting that CNI-1493 is of potentiality for clinical use.