四逆汤对兔髂动脉球囊损伤后血管狭窄和一氧化氮系统的影响

Effects of Sini Decoction on Vascular Stenosis and NO System after Iliac Artery Injured in Rabbits

【目的】通过球囊损伤兔髂动脉造成动脉损伤的动物模型,观察四逆汤对损伤后动脉内膜的保护作用,并探讨四逆汤对一氧化氮(NO)系统的影响。【方法】雄性新西兰大白兔24只,随机分为对照组、模型组、四逆汤治疗组(四逆汤组),每组8只,对照组兔予普通饲料,模型组、四逆汤组兔予以高脂饮食。饲养2周后模型组、四逆汤组兔行髂动脉内膜剥脱术,对照组兔行假手术。术后4周处死各组实验兔,通过透射电镜观察髂动脉内膜的病变情况,并检测兔血清NO水平和总NOS活性;通过免疫组化观察eNOS蛋白在血管壁的表达,RT-PCR方法检测血管壁eNOS mRNA的表达。【结果】模型组兔髂动脉内膜可见大量的泡沫细胞,内皮细胞脱落;而四逆汤组损伤减轻。模型组兔血清NO水平和总NOS活性明显低于四逆汤组和对照组;四逆汤组和对照组eNOS蛋白和eNOS mRNA表达较模型组明显增强,而四逆汤组和对照组之间无显著性差异。【结论】四逆汤可减轻兔髂动脉剥脱术后的内膜损伤,其机制可能与促进髂动脉损伤后内膜eNOS的蛋白和基因的表达,增加NO的产生有关。

[ Objective ] To investigate the effect of Sini Decoction （SND） on preventing vascular stenosis after rabbit iliac artery balloon injury, and the effect of SND on NO system in this procedure. [Method] Twenty-four male New Zealand albino rabbits were equally randomized into control group, model group, and SND group, respectively. Each group contained 8 rabbits. Rabbits of control group were fed with common forage, but model group and SND group fed with high fat diet （1.0% cholesterol, 10% lard）. Two weeks later, the iliac arteries were injured by balloon for model group and SND group. Rabbits were killed four weeks after operation. Serum samples were stored to assay the activity of NOS and levels of NO, Injured iliac artery was fixed by neutral formalin. Protein expression of eNOS in vascular wall was observed through immunohistochemistry method. Iliac artery uhrastructure was investigated by transmission electron microscope. The eNOS mRNA was determined by RT-PCR method. [Results] Transmission electron microscope showed that endothelial cells were desquamated and a great deal of foam cells were found in the model group, while endothelial cells were normal and less foam cells were found in SND group. The serum levels of NO in SND group were higher than that of model group. The serum total NOS activity in SND group was higher than that of model group. Immunohistochemistry showed that expression of eNOS in SND group was stronger than that in model group. RT-PCR results showed that eNOS mRNA expression increased significantly in rabbit iliac artery of SND group than that in model group. [Conclusion] SND can lessen intimal hyperplasia and vascular stenosis in iliac artery injury rabbits, this effect is related with upregulation of eNOS protein and gene and increasing the production of NO in rabbits with iliac artery injury.