一氧化氮对大鼠移植胰腺再灌注损伤的保护作用

Protective effects of Nitric Oxide on the reperfusion injury following pancreaticoduodenal transplantation in rats

目的 探讨一氧化氮 (NO)对大鼠移植胰腺再灌注损伤的保护作用。方法 应用同系大鼠异位全胰十二指肠移植模型 ,大鼠移植术前和术后 5min静脉注射L 精氨酸 (L Arg ,2 0 0mg/kg)和N 硝基 L 精氨酸甲酯 (L NAME ,10mg/kg) ,移植术后 1～ 72h经腹主动脉取血测定大鼠空腹血糖、血清中脂肪酶、淀粉酶及中性粒细胞化学趋化性细胞因子 (CINC)含量 ,测定移植胰腺组织中NO含量、CINCmRNA的表达及髓过氧化酶 (MPO)活性 ,并进行组织学观察。结果 移植胰腺组织中NO含量L Arg组 >对照组 >L NAME组 ;CINC在再灌注后 3h出现峰值 ,L Arg组为(7.66± 1.5 3 ) μg/L ,L NAME组为 (3 4.18± 3 .12 ) μg/L ,对照组为 (2 6.3 1± 2 .0 1) μg/L ,差异有显著性 (P <0 .0 5 ) ;移植物中CINCmRNA于再灌注后 3h表达最强 ,L Arg组表达水平明显低于L NAME组和对照组 ;L Arg组胰小叶间质水肿和胰小叶内中性粒细胞浸润较轻。 结论 外源性应用L Arg或L NAME能够分别增加或减少胰腺组织NO含量 ,NO能抑制CINC的升高及CINCmRNA的表达 ,抑制中性粒细胞浸润 ,对移植胰腺再灌注损伤起保护作用。

Objective To study the protective effects of nitric oxide (NO) on the reperfusion injury following pancreaticoduodenal transplantation in rats.Methods The (homologous) male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used.The L-Arg-treated rats received the intravenous injection of L-Arg 5 mins before and after operation at a dose of 200 mg/kg while the L-NAME-treated rats at a dose of 10 mg/kg.The content of NO in the pancrease graft was measured.Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbant assay,the expression of CINC mRNA detected by Northern blot assay in the pancrease graft,and the activity of myeloperoxidase (MPO) was measured.Histological observation was performed.Results The content of NO in the L-Arg group (0.37±0.09) μmol/L was higher than in the control group (0.28±0.07) μmol/L,while that in the L-NAME group (0.19±0.10) μmol/L was lower than in the control group ( P <0.05).The peak of serum CINC concentration occurred 3 h after reperfusion with the difference among the groups being significiant.The expression peak of CINC mRNA in the pancrease graft occurred 3 h after reperfusion,and the expression level in the L-Arg group was lower in the control group,while that in the L-NAME group was higher than in the control group ( P <0.05).The activity of MPO in the L-Arg group was obviously decreasd as compared with that in the other groups.The pancrease inflammation was ameliorated when L-Arg was administrated,while the pancrease damage was aggravated when L-NAME was administrated.Conclusion L-Arg can increase the content of NO,while LNAME can reduce it.NO can inhibit the elevation of CINC,the CINC mRNA expression and early neutrophil accumulation in the pancreas.NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation.