区域动脉灌注5-FU诱导大鼠急性胰腺炎腺泡细胞凋亡及Caspase-3表达

目的 探讨区域动脉灌注（regional arterial infusion，RAI）5-氟尿嘧啶（5-fluorouracil，5-FU）对大鼠急性胰腺炎（acute pancreatitis，AP）胰腺腺泡细胞凋亡的影响及其对急性胰腺炎的治疗作用。方法 18只健康成年SD大鼠随机分成3组：对照组（C组）、急性胰腺炎组（AP组）和5-FU治疗组（5-FU组）。各组均行胃左动脉置管，AP组和5-FU组以大剂量雨蛙素（每小时腹腔注射50 μg/kg，连续6 h）诱导建立大鼠急性胰腺炎模型，对照组注射同等剂量的生理盐水。5-FU组在第一次腹腔注射雨蛙素1 h后立即区域动脉灌注5-FU（40 mg/kg）治疗，C组和AP组区域动脉灌注等量的生理盐水。建模成功后3 h取标本并处死大鼠，检测血淀粉酶浓度，RT-PCR法检测胰腺组织内TNF-α、IL-1β、IL-6 mRNA表达水平，胰腺标本送病理学检查，Western blotting法检测胰腺组cleaved Caspase-3的蛋白表达，同时TUNEL法检测大鼠胰腺腺泡细胞凋亡情况。结果 与AP组比较，5-FU组血淀粉酶浓度明显降低（P＜0.05）；胰腺组织内TNF-α、IL-1β、IL-6  mRNA表达水平下降（P＜0.05）；胰腺组织病理学改变减轻；胰腺组织cleaved Caspase-3的蛋白表达增加；胰腺腺泡细胞凋亡增加（P＜0.05）。结论 区域动脉灌注5-FU对大鼠急性胰腺炎有改善作用，其作用机制可能与诱导胰腺腺泡细胞凋亡有关。

Effect of 5-fluorouracil administered with regional arterial infusion on pancreatic acinar cell apoptosis and expression of Caspase-3 in rats with acute pancreatitis

Objective To assess the effects of 5-fluorouracil (5-FU) administered with regional arterial infu-sion (RAI) on pancreatic acinar cell apoptosis of acute pancreatitis (AP) and its effect on AP in rats. Methods Eighteen male Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group (C group), acute pancreatitis group (AP group), and the 5-FU treatment group (5-FU group). A catheter was inserted through the left gastric artery in all the three groups. AP model was induced by hourly intraperitoneal injections of saline containing a supramaximally stimulating dose of caerulein (50 μg/kg) for 6 h. 5-FU (40 mg/kg) was administered with RAI to the 5-FU group following 1 h after the first intraperitoneal injection of caerulein. Saline was admin-istered with the same doses to the other two groups. Serum amylase activity and mRNA levels of TNF-α, IL-1β, IL-6 in pancreatic tissues were measured with RT-PCR at 3 h following the induction of AP. The pathological changes in the pancreas tissues were observed and scored. Protein expression of cleaved Caspase-3 in pancre-atic tissues was measured with Western blotting analysis. Apoptosis was quantified by TUNEL assay. Results Compared with the AP group, the serum amylase activity, the mRNA levels of TNF-α, IL-1β, IL-6 in pancreatic tissues and the pathological scores of pancreas in the 5-FU group decreased significantly (P<0.05). Expression of cleaved Caspase-3 in pancreatic tissues and pancreatic acinar cell apoptosis in the 5-FU group increased significantly than that in the AP group (P<0.05). Conclusion RAI with 5-FU has beneficial effects on AP rats, the underlying mechanism is possibly related to indue pancreatic acinar cell apoptosis.nificantly than that in the AP group (P<0.05). Conclusion RAI with 5-FU has beneficial effects on AP rats, the underlying mechanism is possibly related to indue pancreatic acinar cell apoptosis.