Matrix metalloproteinase-9 derived from polymorphonuclear neutrophils increases gut barrier dysfunction and bacterial translocation in rat severe acute pancreatitis
Matrix metalloproteinase-9 derived from polymorphonuclear neutrophils increases gut barrier dysfunction and bacterial translocation in rat severe acute pancreatitis
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DOI：
10.1016/j.surg.2008.08.036
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发表时间：
2009-02-01
期刊：
影响因子：
3.8
通讯作者：
Keck, Tobias
中科院分区：
文献类型：
--
作者：
Mikami, Yukio;Dobschuetz, Ernst V.;Keck, Tobias
背景资料。重症急性胰腺炎(SAP)患者肠屏障功能障碍与中性粒细胞(PMN)及PMN衍生的基质金属蛋白酶-9(MMP9)的关系尚不清楚。本研究旨在探讨中性粒细胞和基质金属蛋白酶-9对大鼠肠屏障功能障碍的影响。用5%牛磺胆酸钠诱导大鼠SAP模型，在急性胰腺炎前48 h和24 h分别注射抗大鼠IIMN血清和BB-94。诱导急性胰腺炎后24小时，通过细菌学、组织学和生化(MPO)分析，观察肠屏障功能障碍及细菌移位(BT)和中性粒细胞移位(PMN)发生率。基质金属蛋白酶-9的抑制是通过耗尽中性粒细胞或用广谱基质金属蛋白酶抑制剂抑制基质金属蛋白酶活性来实现的，并通过酶谱图得到证实。此外，通过自旋陷阱分析对活性氧物种进行了评估。与抗大鼠PMN血清或BB-94治疗组相比，SAP大鼠的黏膜损伤和PMN在肠道组织中的浸润明显增加。SAP组大鼠肠道组织中MMP9和活性氧水平明显高于抗大鼠疼痛血清组和BB-94组。用抗大鼠PMN血清或BB-94预处理可降低SAP中BT的发生率。SAP中BT的发生率可通过PMN的耗尽或通过注射基质金属蛋白酶抑制剂BB-94来预防。中性粒细胞在BT的发生中起着重要的病理生理作用，而基质金属蛋白酶-9参与了BT和PMN在大鼠SAP中的迁移(Surgery 2009；145：147-56。)
Background. The role of polymorphonuclear neutrophil granulocytes (PMNs) and the PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on gut barrier dysfunction in rat SAP.Methods. SAP was induced by the injection of 5% sodium taurocholate, and anti-rat IIMN serum or BB-94 were administered 48 h and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four hours after the induction of acute pancreatitis, the gut barrier dysfunction and, the incidence of bacterial translocation (BT) anti PMN transmigration were investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive oxygen species were evaluated by spin trap assay.Results. The mucosal injury and the infiltration of PMNs into the gut tissue of rats with SAP were significantly increased in comparison with rats treated with anti-rat PMN serum or BB-94. The levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were significantly higher than those of the rats treated with anti-rat PAIN serum or BB-94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in SAP.Conclusion. The incidence of BT in SAP was prevented by the depletion of PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in both BT and PMN transmigration in rat SAP (Surgery 2009; 145:147-56.)