iNOS抑制剂对大鼠胰腺缺血/再灌注损伤的保护作用  

Protcetive effect of iNOS inhibitor on pancreas ischemia/reperfusion injury in rats

作　　者：李柏峰[1] 刘永锋[1] 夏丽萍[2] 程颖[1] 成东华[1] 王晓东[3] 李铁民[1] 赵宁[1] 

机构地区：[1]中国医科大学附属第一医院普外一科暨器官移植科,辽宁省沈阳市110001 [2]中国医科大学附属第一医院风湿免疫科,辽宁省沈阳市110001 [3]沈阳市第四人民医院普外科,辽宁省沈阳市110031

出　　处：《世界华人消化杂志》2005年第1期44-48,共5页World Chinese Journal of Digestology

基　　金：辽宁省重大项目资助项目;No.00225001

摘　　要：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.AIM: To investigate the effect of inducible nitric oxide syn-thase (iNOS) inhibitor animoguanidine (AG) during is-chemia/reperfusion (I/R) in rat pancreas. METHODS: The models of sham-operation and pancreas ischemia were established in rats. The splenic artery of rats in I/R group was occluded reversibly by microsurgical clip for 30 minutes, and the animals were killed after 2,4,6, 12, or 24 hours of reperfusion. Aminoguanidine was given to the rats in AG group (40, 60, 80 mg/kg; iv). Rats in control group received saline only. The serum nitric oxide (NO) level and amylase activity were detetermined with nitrate reduc-tase and iodine-starch chromatometry. Pancreas constitutive NOS (cNOS) and iNOS activities were measured using NOS Test Kit. Pancreas sections were evaluated by light microscopy after HE and immunohistochemistry staining. RESULTS: In I/R group, serum NO level and amylase activity were increased significantly after 4-hour reperfusion. The NO level reached the peak and the amylase activity began to rise at 4 hour. After the administration of aminoguanidine (80 mg/kg), the NO level and amylase activity became much lower than those in the I/R group (P<0.01). After 4-hour reperfusion, tissue iNOS activity was increased significantly in I/R group, but remained normal in AG group (P<0.01). Six, twelve, and twenty-four hours after reperfusion, pancreas injury was observed in I/R group, but no siginificant changes occurred in pancreas after animoguanidine (80 mg/kg) administration. Four hours after reperfusion, the positive rate of iNOS in the specimens from I/R group was significantly higher than that in AG (80 mg/kg) group (439±127 vs 33±4, P<0.01). The activity of cNOS showed no significant difference between any two groups. CONCLUSION: Selective iNOS inhibitor aminoguanidine has protective effect against the ischemia/reperfusion injury in rat pancreas.

关 键 词：再灌注损伤 胰腺缺血 INOS抑制剂 大鼠 NO水平 氨基胍 保护作用 淀粉酶活性 结论 等量 

分 类 号：R576[医药卫生—消化系统]