氨基胍对大鼠胰腺移植保护作用的实验研究  

Protective effect of aminoguanidine on transplanted pancreas in rats

作　　者：李柏峰[1] 张克忠[1] 刘永锋[1] 程颖[1] 成东华[1] 李铁民[2] 

机构地区：[1]中国医科大学附属第一医院器官移植科,辽宁沈阳110001 [2]中国医科大学附属第一医院干部诊疗科,辽宁沈阳110001

出　　处：《中国普通外科杂志》2008年第3期237-241,共5页China Journal of General Surgery

基　　金：辽宁省重大科技资助项目(00225001)

摘　　要：目的探讨诱导型一氧化氮合酶抑制剂氨基胍对大鼠移植胰腺的保护作用。方法糖尿病大鼠模型30只随机分成3组:(1)空白对照组(n=6),仅开腹手术,不作移植;(2)移植对照组(n=6),仅作胰腺移植;(3)氨基胍处理组(n=18),移植胰腺恢复血运前经阴茎背静脉注入盐酸氨基胍(AG)溶液,剂量分别为60,80,100mg/kg。再灌注4h后检测血清一氧化氮(NO)水平,血糖以及淀粉酶活性,定量分析胰腺组织中的结构型一氧化氮合酶(cNOS)和诱导型一氧化氮合酶(iNOS)活性,并对胰腺进行组织形态学和组织化学检查。结果与移植对照组比较,氨基胍处理组血NO水平及淀粉酶活性明显降低,胰腺病理损害较轻,其中以AG80mg/kg亚组效果更显著(P<0.01),且该亚组血糖及iNOS活性与表达也明显低于移植对照组(P<0.01)。结论诱导型一氧化氮合酶选择性抑制剂氨基胍在大鼠胰腺移植中起到保护作用。其作用机制可能与抑制NO的过量产生,减轻其作为自由基的细胞毒性有关。Objective To investigate the effect of inducible nitric oxide synthase inhibitor aminoguanidine on transplanted pancreas in rats. Methods The models of pancreas transplantation were established in 30 rats. The streptozotocin induced diabetic male Wistar rats were randomly assigned to 3 groups： （ 1 ） Blank control group （ n = 6 ） , the rats underwent shamsurgery ; （ 2 ） transplant control group （ n = 6 ） , the rats received pancreas transplantation only ; （ 3 ） aminoguanidine group （ AG group ） （ n = 18 ） , aminoguanidine （ a dose of 60, 80, or 100 mg/kg weight） was added to the intravascular infusion before reperfusion of the transplanted pancreas. At 4 h after reperfusions, serum nitric oxide （ NO ） level, blood sugar, and amylase activity were detected, cNOS and iNOS activity of pancreas were detected Pancreas sections were evaluated by light microscopic examination with HE staining and immunohistochemistry staining. Results As compared with transplant control group, the serum NO level and amylase activity decreased significantly, and pancreas injury was much less in AG groups, especial in AG-80 mg/kg sub-group showed the most significant difference （P 〈0.01 ）. The expression and activity of tissue iNOS activity, and blood sugar in AG-80 mg/kg sub-group were much lower than those in transplant control group （ P 〈 0. 01 ）. Conclusions Selective iNOS inhibitor-aminoguanidine has protective effect on the transplanted pancreas in rats. The possible mechanisms may be inhibition of overproduction of NO, and reduction the cytotoxicity as free radicals of NO.

关 键 词：胰腺移植 缺血再灌注 诱导型—氧化氮合酶 氨基胍 

分 类 号：R322.57[医药卫生—人体解剖和组织胚胎学] R617[医药卫生—基础医学]