氨基胍对大鼠胰腺移植保护作用的实验研究

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60，80，100 mg/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AG 80 mg/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。

Protective effect of aminoguanidine on transplanted pancreas in rats

Abstract: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 4h 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.