首页> 中文期刊> 《肝胆胰外科杂志》 >区域动脉灌注5-FU改善大鼠重症急性胰腺炎相关的肺损伤

区域动脉灌注5-FU改善大鼠重症急性胰腺炎相关的肺损伤

             

摘要

Objective To assess the effects of 5-fluorouracil (5-FU) administered with regional arterial infu-sion (RAI) on severe acute pancreatitis (SAP) associated acute lung injury (ALI) in rats and to explore the under-lying mechanisms. Methods Thirty-six male Sprague-Dawley (SD) rats were randomly divided into 3 groups:control group (C group), severe acute pancreatitis group (SAP group), and 5-FU administered with regional arte-rial infusion group (5-FU group). SAP model was induced by 5% sodium taurocholate (1 mL/kg) injected into the pancreatic duct. 5-FU (40 mg/kg) was immediately administered with RAI to the 5-FU group following the establishment of the SAP model. Saline was administered the same way to other two groups. The pathological changes in the pancreas and lungs were observed and scored. Serum amylase activity, lung wet/dry weight ratio, lung myeloperoxidase (MPO) activity, and the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the serum were measured at 12 h and 24 h following the induction of SAP. Results Compared with the control group, the serum amylase activity, the levels of TNF-α, IL-1β and IL-6 in the serum, lung wet/dry weight ratio, lung MPO activity, as well as the pathological scores of lungs for both the SAP group and the 5-FU group increased significantly (P<0.05). However, compared with the SAP group at 12 and 24 h, all those parameters were attenuated in the 5-FU group (P<0.05). Acute lung injury was observed in SAP group under light microscope. The RAI with 5-FU attenuated the SAP associated acute lung injury and decreased the pathological scores of lungs. Conclusion 5-FU has beneficial effects on SAP associated acute lung injury in rats, which mechanism possibly involves the alleviation the overexpression of proinflammatory cytokines.%目的研究区域动脉灌注(regionalarterialinfusion,RAI)5-氟尿嘧啶(5-fluorouracil,5-FU)对大鼠重症急性胰腺炎(severeacutepancreatitis,SAP)相关的急性肺损伤(acutelunginjury,ALI)的作用及其可能的机制。方法36只健康成年雄性SD大鼠随机分成3组:对照组(C组)、胰腺炎组(SAP组)、区域动脉灌注5-FU治疗组(5-FU组)。逆行胰胆管注射5%牛磺胆酸钠(1mL/kg)建立SAP模型。5-FU组在诱导SAP模型后立即行区域动脉灌注5-FU(40mg/kg)治疗,C组和SAP组区域动脉灌注等量的生理盐水。建模成功后分别于12、24h取标本并处死大鼠,胰腺和肺脏组织送病理学检查,检测肺组织湿干比,肺组织髓过氧化物酶(myeloperoxidase,MPO)活性,血淀粉酶和血中TNF-α、IL-1β、IL-6的含量。结果与C组比较,SAP组与5-FU组血淀粉酶、血中促炎细胞因子(TNF-α、IL-1β、IL-6)、肺组织湿干比、肺组织MPO均显著升高(P<0.05);与SAP组比较,5-FU组上述指标均显著下降(P<0.05)。光镜下可见SAP组出现明显的肺损伤,5-FU区域灌注治疗后肺损伤减轻,病理学评分下降。结论区域动脉灌注5-FU对大鼠重症急性胰腺炎相关的急性肺损伤有改善作用,其作用机制可能与抑制促炎细胞因子的过度表达有关。

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