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目的阐明急性坏死性胰腺炎(ANP)并多器官功能障碍综合征(MODS)大鼠模型腹腔内压(IAP)、肠屏障功能及炎症因子的动态变化及规律,并探讨其早期治疗窗。方法 100只雌性SPF级大鼠随机分为假手术组(SO组,n=40)、ANP组(n=40)及空白对照组(基线组,0 h,n=20),其中ANP组采用胰胆管内逆行注入4.5%牛磺胆酸钠(1 ml/kg)诱导ANP并MODS模型。术后3、6、12、24 h分批处死大鼠并收取标本,测定IAP、腹水量、血淀粉酶、血肌酐(Cr)、总胆红素(TB)、肿瘤坏死因子-α(TNF-α)、二胺氧化酶(DAO)、D-乳酸(D-Lat)水平并进行胰腺和小肠病理评分。测量的数据均采用方差分析进行比较。结果 (1)ANP组的IAP呈持续升高的趋势,在3、6、12、24 h时点均高于SO组2~3倍[(6.1±1.6)mm Hg vs.(2.0±0.7)mm Hg,(12.0±2.2)mm Hg vs.(0.7±0.3)mm Hg,(13.8±1.5)mm Hg vs.(1.5±0.7)mm Hg,(14.6±1.7)mm Hg vs.(2.2±1.4)mm Hg,均P<0.05],且6 h为升高幅度的峰值;(2)ANP组的血淀粉酶、Cr、TB、TNF-α、DAO、D-Lat随病程发展逐渐升高,且在3、6、12、24 h时点均明显高于SO组(均P<0.05),其中TNF-α、DAO、D-Lat的升高幅度的峰值亦出现在6 h。结论 ANP并MODS模型的IAP、肠屏障功能及炎症因子在建模后6 h达到变化幅度的峰值,提示6 h可能为ANP的早期治疗窗。
Objective To clarify the dynamic changes and regularities of intra-abdominal pressure (IAP), intestinal barrier function and inflammatory cytokines in acute necrotizing pancreatitis (ANP) and multiple organ dysfunction syndrome (MODS) rats and to explore its early treatment window. Methods 100 female SPF rats were randomly divided into sham operation group (SO group, n = 40), ANP group (n = 40) and blank control group (baseline group, 0 h, n = 20) ANP and MODS models were induced by retrograde injection of 4.5% sodium taurocholate (1 ml / kg) into the pancreatic duct. The rats were sacrificed 3, 6, 12 and 24 h after operation. The levels of IAP, ascites, serum amylase, serum creatinine (Cr), total bilirubin (TB), tumor necrosis factor-α -α), diamine oxidase (DAO), D-lactate (D-Lat) were measured and pathological scores of pancreas and small intestine were measured. The measured data were compared using analysis of variance. Results (1) The IAP of ANP group showed a trend of increasing continuously, which was 2 ~ 3 times higher than that of SO group at 3, 6, 12 and 24 hours [(6.1 ± 1.6) mmHg vs. (2.0 ± 0.7) (12.0 ± 2.2) mm Hg vs. (0.7 ± 0.3) mm Hg, (13.8 ± 1.5) mm Hg vs. (1.5 ± 0.7) mm Hg, (14.6 ± 1.7) mm Hg vs. (2.2 ± 1.4) ) mmHg, all P <0.05], and the peak value of 6 h increased; (2) The levels of serum amylase, Cr, TB, TNF-α, DAO and D-Lat in ANP group increased gradually with the course of disease, And at 3, 6, 12 and 24 hours, they were all significantly higher than those in SO group (all P <0.05). The peak of TNF-α, DAO and D-Lat increase also appeared at 6 hours. Conclusion The IAP, intestinal barrier function and inflammatory cytokines in ANP and MODS model reached the peak value of change 6 h after modeling, suggesting that 6 h may be the early therapeutic window of ANP.