诱导型一氧化氮合酶与移植血管平滑肌细胞增生的关系

Relationship of Vascular Smooth Muscle Cells Hyperplasia of Vein Graft and Inducible Nitric Oxide Synthase

目的 探讨诱导型一氧化氮合酶 (iNOS)与移植血管平滑肌细胞增生的关系。方法 新西兰大白兔 15只随机分成 3组 ,建立双侧颈动脉间置移植颈外静脉的动物模型。高剂量组每日喂食L 精氨酸 (L Arg) 2 5 0mg/kg ,低剂量组每日喂食L Arg 12 5mg/kg ;对照组不喂食L Arg ,持续 2周。检测血浆和组织匀浆一氧化氮(NO)水平 ,移植血管iNOSmRNA表达。观察术后 3和 6周移植血管平滑肌细胞增生。结果 1.iNOS活性 :(1)血浆NO水平 :实验组血浆NO水平显著高于对照组 ,高剂量组血浆NO水平高于低剂量组 ;(2 )组织匀浆一氧化氮合酶 (NOS)活性 :实验组组织匀浆NOS活性显著高于对照组 ;(3)组织匀浆iNOSmRNA表达 :术后 3周实验组iNOSmRNA表达 ,对照组无表达 ;术后 6周实验组iNOSmRNA表达高于对照组 ,高剂量组高于低剂量组。 2 .移植血管平滑肌细胞形态学变化 :(1)SMA免疫组化染色 :实验组移植血管平滑肌细胞厚度低于对照组 ;术后 6周低剂量组移植血管平滑肌细胞厚度低于高剂量组 ;(2 )PCNA免疫组化染色 :术后 3周实验组平滑肌细胞增殖低于对照组 ;术后 6周低剂量组平滑肌细胞增殖低于对照组和高剂量组。结论 iNOS表达致体内NO水平增高可抑制移植血管平滑肌细胞增生 ;

Purpose. To research the relationship of vascular smooth muscle cells hyperplasia of vein graft and inducible nitric oxide synthase. Methods. Fifteen New Zealand rabbits were divided into 3 groups randomly. Every rabbit was operated under microscope, placed one side external jugular vein into the same side common carotid artery by end-to-end anastomy, and both sides were operated at the same time. L-Arg was given through oral method since the operative day for 2 weeks according to the following dosage: group A 0 mg/kg, group B 125 mg/kg, group C 250 mg/kg. Nitric oxide of plasma and tissues were analysised and the expression of iNOS mRNA of vein graft were detected by RT-PCR 3 and 6 weeks after operation, PCNA of VSMCs in vein graft were analysised by immunohistochemistry method. Results. 1. Activity of iNOS: (1) Concentration of plasma NO: The concentration of plasma NO of group B and C were significantly higher than that of group A, and the concentration of group C was higher than that of group B; (2) The activity of NOS: the activity of group B and C were significantly higher than that of group A, (3)iNOS mRNA: the iNOS mRNA of vein graft was expressed 3 weeks postoperatively in both group B and C. Both the expression of group B and C were significantly higher than that of group A, and the the expression of group C was higher than that of group B 6 weeks postoperatively. 2. Morphologic changes of vein graft: (1)SMA: the VSMCs thickness of vein graft of group B and C were significantly thinner than that of group A, and the VSMC thickness of vein graft of group B was significantly thinner than that of group C 6 weeks postoperatively; (2) PCNA: The hyperplasia of VSMCs of group B and C was lower than that of group A 3 weeks after operation. The hyperplasia of VSMCs of group B was lower than that of group A and C 6 weeks postoperatively. Conclusions. The VSMCs hyperplasia of vein graft can be inhibited by NO which increased by the appropriate expression of iNOS. The hyperplasia is related to the concentration of NO.