连续性血液净化对急性重症胰腺炎早期诱导的肠黏膜屏障功能障碍的影响

Effects of continuous blood purification therapy on early induced gut mucosal dysfunction in patients with severe acute pancreatitis

目的研究连续性血液净化(continuous blood purification,CBP)对急性重症胰腺炎(severe acute pancreatitis,SAP)早期诱导的肠黏膜屏障功能障碍的作用。方法以26例行持续静静脉血液滤过(continuous veno-venous hemofiltration,CVVH)的早期SAP患者作为研究对象。所有患者行CVVH24h,以血清D-乳酸、二胺氧化酶(diamine oxidase,DAO)和内毒素水平以及肠黏膜上皮细胞的通透性作为评价肠黏膜屏障功能的指标。分别在治疗前和治疗6、12和24h时采集静脉血。同时培养人Caco-2细胞,建立单层肠黏膜上皮细胞模型并与SAP患者CVVH各时间点的血清混合培养,电阻仪测定跨细胞电阻以反映其通透性的变化,荧光显微镜观察骨架蛋白(纤维状肌动蛋白)的分布和表达。结果 CVVH治疗后急性生理学与慢性健康状况评分Ⅱ显著改善。与正常对照组比较,SAP患者血清二胺氧化酶、D-乳酸和内毒素水平及通透性明显增高(P<0.01),骨架蛋白模糊,部分断裂,细胞间连接松散。CVVH治疗后SAP患者血清二胺氧化酶、D-乳酸和内毒素水平明显下降(P<0.01),肠黏膜上皮细胞的高通透性和骨架蛋白解聚得以减轻。结论 SAP患者早期存在肠黏膜屏障功能障碍。CBP不仅改善全身机能状况而且对SAP诱导的肠黏膜屏障功能障碍具有保护作用。这种作用与清除炎症因子并改善上皮细胞骨架蛋白的重排有关。

Objective Early gut mucosal dysfunction is one of the critical pathophysiological disorders in patients with severe acute pancreatitis（SAP）.To investigate the effects of continuous blood purification on SAP induced gut mucosal dysfunction,we conducted a prospective study in 26 patients with SAP.Method All patients were treated with continuous veno-venous hemofiltration（CVVH） for 24 hours.Permeability of the epithelial monolayer,serum concentrations of diamine oxidase（DAO）,D-lactate and endotoxin were used as the markers for the assessment of epithelial function.Blood samples were taken from the patients at 0,6,12 and 24h during CVVH.Serum DAO,D-lactate and endotoxin were determined by spectrophotometry.Monolayer Caco-2 cells incubated with patient＇s serum were used as the model to assess SAP-induced epithelial permeability changes by measuring their trans-epithelial electric resistance（TEER）.Expression and distribution of actin in the cells were observed by immunofluorescence.Result The Acute Physiology and Chronic Healthy Evaluation（APACHE） ？ score was significantly improved after CVVH.Compared with the normal controls,SAP patients showed the increase of serum DAO,D-lactate,endotoxin and epithelial permeability.Peripheral filament bands in the cells became blurred,with loose cell-cell junctions.After CVVH,serum DAO,D-lactate and epithelial permeability decreased,and the organization of actin improved in all patients.Conclusion Early gut mucosal dysfunction is present in SAP patients.CVVH improves patients＇ general conditions as well as their gut mucosal dysfunction,probably resulting from the clearance of over-expressed pro-inflammation cytokines and reorganization of actin in epithelial cells.