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目的:探讨选择性诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)在大鼠胰腺缺血/再灌注损伤(I/R)中的作用. 方法:建立大鼠胰腺缺血/再灌注模型.I/R组胰腺缺血30 min,再灌注时间分别为2、4、6、12、24 h;AG组静脉注射氨基胍(40、60、80 mg/kg);对照组注射等量的生理盐水.使用硝酸还原酶法和碘-淀粉比色法分别检测血清一氧化氮(NO)水平及淀粉酶活性随再灌注时间的变化,定量分析结构型一氧化氮合酶(cNOS)和诱导型一氧化氮合酶(iNOS)在胰腺组织中的活性,并对胰腺进行组织形态学检查和免疫组化分析. 结果:I/R组血清NO水平和淀粉酶活性明显升高,再灌注4 h后NO水平达到高峰,淀粉酶活性开始升高;AG 组血清NO水平及淀粉酶活性低于I/R组(P<0.01).I/R 组再灌注4 h后iNOS活性显著增强,AG组iNOS活性明显下降(P<0.01).再灌注6 h后I/R组开始出现胰腺损伤的表现,AG组未见胰腺组织明显损害表现.再灌注4 h后I/R组见iNOS强阳性染色,AG组中未见iNOS阳性染色,二者比较有显性差异(4391±127 vs 33±4,P<0.01). 结论:选择性iNOS抑制剂氨基胍在大鼠胰腺缺血/再灌注中起到保护作用.
Objective: To investigate the effect of selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on rat pancreatic ischmia / reperfusion injury (I / R) .Methods: Reperfusion model.Intra pancreatic ischemia in I / R group for 30 min, reperfusion time were 2,4,6,12,24 h; AG group intravenous aminoguanidine (40,60,80 mg / kg); control group injected The same amount of normal saline.Nitric acid reductase and iodine-starch colorimetric method were used to detect the level of serum nitric oxide (NO) and the change of amylase activity with the reperfusion time, the quantitative analysis of structural nitric oxide synthase (cNOS ) And inducible nitric oxide synthase (iNOS) activity in pancreatic tissue, and histopathological examination and immunohistochemical analysis of the pancreas.Results: Serum NO levels and amylase activity were significantly increased in I / R group, After 4 h of reperfusion, the NO level peaked and the amylase activity began to increase. The serum NO level and amylase activity in AG group were lower than those in I / R group (P <0.01) , The activity of iNOS in AG group decreased significantly (P <0.01), and the pancreas injury began to appear in I / R group 6 h after reperfusion, and no obvious damage of pancreatic tissue was found in AG group. INOS positive staining was observed in I / R group after 4 h of perfusion, but iNOS positive staining was not observed in AG group (4391 ± 127 vs 33 ± 4, P <0.01) .Conclusion: Selective iNOS inhibition Aminoguanidine plays a protective role in rat pancreatic ischemia / reperfusion.