单核细胞趋化蛋白-1与急性胰腺炎肠屏障功能呈负相关

Monocyte Chemoattractant Protein-1 Correlates Negatively with Intestinal Barrier Function in Acute Pancreatitis

背景：急性胰腺炎（AP）时可发生全身性炎症反应综合征，肠屏障功能障碍是导致重症急性胰腺炎（SAP）并发多器官功能衰竭的重要因素之一。目的：检测大鼠AP模型单核细胞趋化蛋白-1（MCP-1）表达和肠屏障功能指标的变化，探讨MCP-1在AP肠屏障功能障碍中的作用。方法：分别以0．5％和5％牛磺胆酸钠逆行胰胆管注射制备大鼠急性水肿性胰腺炎（AEP）和急性坏死性胰腺炎（ANP）模型，行胰腺组织病理学评分，电子显微镜观察回肠组织超微结构，免疫组化染色、RT—PCR和蛋白质印迹法检测回肠组织中紧密连接蛋白occludin和MCP-1的表达。结果：与假手术（SO）组相比，AP模型大鼠尤其是ANP组大鼠胰腺组织病理学评分显著升高，回肠绒毛高度和柱状细胞指数降低，occludin表达下调（P〈0．05）。SO组和AEP组回肠组织中无MCP-1表达，ANP组MCP-1表达随时间延长而上调（P〈0．05）。回肠组织MCP-1表达与胰腺组织病理学评分呈正相关，与肠屏障功能指标（绒毛高度、柱状细胞指数和occludin表达）呈负相关。结论：ANP大鼠回肠组织中MCP-1表达上调，MCP-1在AP肠屏障功能障碍中发挥重要作用。

Background： Systemic inflammatory response syndrome can occur in acute pancreatitis （AP）, and intestinal barrier dysfunction is a crucial factor in the occurrence of multiple organ failure in severe acute pancreatitis （SAP）. Aims： To investigate the expression of monocyte chemoattractant protein-1 （MCP-1） and the changes of intestinal barrier function in rat AP model, and to assess the effect of MCP-1 on intestinal barrier dysfunction in AP. Methods： Rat models with acute edematous pancreatitis （AEP） and acute necrotizing pancrcatitis （ANP） were induced by retrograde injection of 0.5% and 5% sodium taurocholate, respectively. The severity of pancreatitis was assessed by pancreatic histopathologic score, the ileal ultrastructural changes were observed by electron microscopy, and the expressions of tight junction protein occludin and MCP-1 in ileal tissues were determined by immunohistochemical staining, RT-PCR and Western blotting. Results： Compared with sham operation （SO） group, the pancreatic histopathologic score elevated significantly and the height of villi, index of columnar cells and expression of occludin in ileal tissues decreased significantly in AEP and ANP groups （P〈0.05）, particularly in ANP group. MCP-1 expression was absent in ileal tissues of SO and AEP groups, but was upregulated in ANP group in a time-dependent manner （P〈0.05）. Expression of MCP-1 in ileal tissues correlated positively with pancreatic histopathologic score and negatively with markers of intestinal barrier function such as height of villi, index of columnar ceils and expression of occludin. Conclusions： MCP-1 is upregulated in ileal tissues of ANP rats and might play an important role in intestinal barrier dysfunction in AP.