摘要
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50μg/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 m RNA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-6m RNA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。
objective To assess the effects of 5-fluorouracil（5-FU） administered with regional arterial infusion（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 administered with the same doses to the other two groups. Serum amylase activity and m RNA 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 pancreatic tissues was measured with Western blotting analysis. Apoptosis was quantified by TUNEL assay. Results Compared with the AP group, the serum amylase activity, the m RNA 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 sig-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.
出处
《肝胆胰外科杂志》
CAS
2016年第3期205-208,共4页
Journal of Hepatopancreatobiliary Surgery
基金
浙江省自然科学基金(LY12H03007)
国家自然科学基金(81370563)
浙江省医药卫生重大科技计划(WKJ2012-2-033)
浙江省科技厅公益性应用项目(2012C23108))
温州市科技局项目(H20110016)
