L-精氨酸、氨基胍和胍丁胺在大鼠局灶性脑缺血再灌注损伤中的作用

Effect of L-arginine,aminoguanidine and agmatine on focal cerebral ischemia-reperfusion injury in rats

目的:观察L-精氨酸(L-Arg)、氨基胍(AG)和胍丁胺(AGM)对大鼠局灶性脑缺血组织中一氧化氮(NO)含量的影响,探讨3种药对脑缺血再灌注损伤大鼠是否具有保护作用和NO在脑缺血再灌注损伤的作用及机制。方法:线栓法建立大鼠局灶性脑缺血(MCAO)模型,大鼠行为学改变用Longa评分标准来评价,血清NO浓度用酶标仪检测,脑内诱导型一氧化氮合酶(iNOS)用免疫组织化学方法测定。结果:与假手术组相比,模型组、L-Arg组、AG组和AGM组在缺血再灌注12、24、72 h的NO含量均显著增加(P<0.05);与模型组相比,在缺血再灌注12 h,L-Arg组行为学评分显著降低(P<0.05),NO含量显著升高(P<0.05);在缺血再灌注24 h,AG组和AGM组行为学评分显著降低(P<0.05),NO含量也显著降低(P<0.05)。在缺血再灌注12、24、72 h,L-Arg组的iNOS阳性细胞数与模型组相比无显著差异(P>0.05);而AG组和AGM组则均显著低于模型组(P<0.05)和L-Arg组(P<0.05)。结论:脑缺血再灌注损伤后血清NO和海马内iNOS的表达随时间有动态变化。L-Arg在术后12 h、AG和AGM在术后24h对局灶性脑缺血再灌注损伤大鼠有保护作用。

AIM：To investigate the protective effects of L-arginine（L-Arg）,aminoguanidine（AG） and agmatine（AGM） on cerebral ischemia-reperfusion injury and to evaluate the role of NO in cerebral ischemic injury.METHODS： The suture-occluded method was used in rats to establish the animal model of middle cerebral artery occlusion（MCAO）.The neurobehavioral changes were evaluated by Longa scoring.The content of NO in serum was determined with microplate reader.The activity of iNOS in the focal ischemic cerebral tissues at the scheduled time was assayed by immunohistochemical method.RESULTS： （1） Compared to sham-operation group,the NO content significantly increased（P0.05） in the MCAO rats after reperfusion for 12 h,24 h and 72 h following ischemia.（2） Compared to ischemic group,the neurobehavioral scores in L-Arg group significantly decreased（P0.05） after reperfusion for 12 h following ischemia and the NO content increased（P0.05）.After reperfusion for 24 h following ischemia,the neurobehavioral scores and the NO content in both AG group and AGM group significantly decreased（P0.05）.After reperfusion for 12 h,24 h and 72 h following ischemia,the iNOS-positive cells in L-Arg group had no statistical difference（P0.05）,but those in AG group and AGM group was lower than those in ischemic group（P0.05） and L-Arg group（P0.05）.CONCLUSION： The contents of NO in serum and expression of iNOS in the focal ischemic cerebral tissues have dynamic changes with the time course of ischemia-reperfusion injury.Administration of L-Arg,AG or AGM has beneficial effect on the animals with cerebral ischemia-reperfusion.