慢性肾脏疾病促进大鼠颈动脉球囊损伤模型中新生内膜的增生

Chronic kidney disease increases neointima hyperplasia in rat with carotid artery balloon injury

目的探讨慢性肾脏疾病(chronic kidney disease,CKD)促进大鼠颈动脉球囊损伤模型中新生内膜的增生机制。方法将SD大鼠分为3组,分别接受:(1)实验组(5/6肾脏切除术+右侧颈总动脉球囊损伤+左侧颈总动脉球囊损伤假手术),取右侧颈总动脉测量;(2)假手术组(5/6肾脏切除假手术+右侧颈总动脉球囊损伤+左侧颈总动脉球囊损伤假手术),取右侧颈总动脉测量;(3)对照组(5/6肾脏切除术+右侧颈总动脉球囊损伤+左侧颈总动脉球囊损伤假手术),取左侧颈总动脉测量。同时,设计C-反应蛋白(空白组、C-反应蛋白50μg/mL组、C-反应蛋白100μg/mL组)刺激大鼠主动脉平滑肌细胞(RASMC)实验,探究其对单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)mRNA、中性粒细胞趋化因子(cytokine-induced neutrophilchemoattractant,CINC)-2 mRNA表达的影响。结果与假手术组、对照组相比,实验组的新生内膜面积[(0.101±0.022)mm^2vs.(0.004±0.002)mm^2vs.(0.338±0.040)mm^2,P<0.05]、新生内膜面积/中膜面积(0.718±0.152vs.0.017±0.006 vs.1.267±0.141,P<0.05)明显增加,差异有统计学意义。当C-反应蛋白浓度由0μg/mL(空白组)、50μg/mL、100μg/mL依次变化时,MCP-1 mRNA、CINC-2 mRNA的表达增加,差异有统计学意义(P<0.05)。结论在大鼠颈动脉球囊损伤的动物模型中,CKD促进了颈动脉新生内膜的增生,但若没有球囊损伤,CKD在此实验条件下不足以使颈动脉新生内膜有明显的增生。此浓度下的C-反应蛋白刺激可以使大鼠主动脉平滑肌细胞中MCP-1 mRNA、CINC-2 mRNA的表达增加,其可能是CKD促进颈动脉新生内膜增生的机制之一。

Objectives To explore the mechanism of chronic kidney disease(CKD)promoting the proliferation of neointima in rats with carotid artery balloon injury.Methods The SD rats were divided into 3 groups as following:(1)treatment group[5/6 nephrectomy+right carotid artery(RCA)balloon injury+left carotid artery(LCA)balloon injury sham,take RCA measurement];(2)sham group(5/6 nephrectomy sham+RCA balloon injury+LCA balloon injury sham,take RCA measurement;(3)control group(5/6 nephrectomy+RCA balloon injury+LCA balloon injury sham,take LCA measurements).At the same time,C-reactive protein(CRP)(3 groups:Veh group,CRP 50μg/mL group,CRP 100μg/mL group)were designed to stimulate the rat aortic smooth muscle cells(RASMC)to explore its effect on the expression of monocyte chemoattractant protein-1(MCP-1)mRNA and cytokine-induced neutrophil chemoattractant(CINC)-2 mRNA.Results Compared with sham group and control group,neointima[(0.101±0.022)mm2 vs.(0.004±0.002)mm2 vs.(0.338±0.040)mm2,P<0.05]and neointima/media(0.718±0.152 vs.0.017±0.006 vs.1.267±0.141,P<0.05)in treatment group were significantly increased.Expression of MCP-1 mRNA and CINC-2 mRNA increased as CRP concentration changed from 0μg/mL(Veh)to 50μg/mL to 100 g/mL(P<0.05).Conclusions In our carotid artery balloon injury models of rats,CKD can promote carotid neointima hyperplasia,but without balloon injury,CKD is not enough to promote the carotid neointima hyperplasia obviously under this experimental condition.With the stimulation of CRP at this concentration can increase the expression of MCP-1 mRNA and CINC-2 mRNA in RASMC,which may be one of the mechanisms of CKD promoting the proliferation of neointima in carotid artery.