NO在实验性大鼠颈动脉瘤发展中的作用

目的建立一种新的颈动脉动脉瘤模型,观察iNOS在实验性动脉瘤组织局部的表达情况和选择性iNOS抑制剂氨基胍对动脉瘤增大和对血清NO水平的影响。方法50只SD大鼠随机分为3组,应用弹性蛋白酶灌注颈总动脉建立颈动脉梭形动脉瘤模型。A组给予氨基胍干预;B组给予生理盐水;C组为阴性对照。测量颈总动脉直径和血清硝酸盐含量。应用HE、免疫组化和原位杂交评价动脉瘤的病理特征和iNOS的局部表达特点。结果选择性iNOS抑制剂可以明显抑制动脉瘤增大的程度和血清硝酸盐水平。诱导的动脉瘤病理特征和外形与人动脉瘤组织相似,主要表现为动脉瘤壁明显增厚,内弹力膜和弹性膜全部消失,平滑肌细胞层变薄和消失。中膜和外膜管壁大量的炎症细胞浸润,氨基胍明显抑制iNOS的表达。结论应用弹性蛋白酶灌注颈动脉可以在大鼠诱导出梭形动脉瘤。动脉瘤的增大与局部升高的NO有关。

EFFECTS OF NITRIC OXIDE ON THE DEVELOPMENT OF EXPERIMENTAL CAROTID ANEURYSM IN RATS

Objective To develop a new carotid aneurysmal model in rats,and to investigate iNOS expression,NO production and the effects of selective inhibition of iNOS by aminoguanidine during the growth of experimental carotid aneurysm.Methods Fifty adult male SD rats(250-300g)were randomly divided into 3 groups.The carotid fusiform aneurysmal model was created by a catheter-directed elastase infusion into the isolated right common carotid artery segment.Each rat received an intraperitoneal injection of aminoguanidine (group A,n=20) or normal saline(group B,n=20) in the morning from postoperative day(POD)1 through POD 14.Group C served as the control group(n=10),receiving intra-aortic normal saline infusion.Catotid diameter and nitrate levels were measured.Pathological features and iNOSexpression in the aneurysmalwall were evaluated by hematoxylin-eosin,in situ hybridization and immunohistochemical analysis.Results Selective inhibition of iNOS could significantly suppress the growth of carotid aneurysm and the serum level of nitrate.The pathological features of experimental coratid aneurysm showed that the artery wall became significantly thick.The tunica intima,the elastic and muscular layers were disrupted or disappeared,which were similar to the natural aneurysm.There were significant infiltrating inflammatory cells in tunica intimaand muscular layers.Aminoguanidine could suppress the expression of iNOS.Conclusion Coratid fusiform aneurysm can be induced in rats by elastaseinfusion.The growth of aneurysm is influenced by local expression of iNOS and high levels of NO in the artery.