依维莫司对大鼠颈总动脉球囊损伤后血管再狭窄的影响

Effect of Everolimus on vascular restenosis in rats with injured carotid artery by balloon

目的建立大鼠颈动脉球囊损伤模型,观察依维莫司对大鼠颈动脉球囊损伤后再狭窄的影响。方法 36只雄性SD大鼠随机分为对照组、损伤组和药物组,每组各12只。损伤组和药物组均应用球囊损伤左侧颈总动脉,药物组术前1天开始每天给予依维莫司1.5 mg/kg灌胃,术后连续28 d给予0.75 mg/kg,对照组及损伤组给予等量生理盐水灌胃。28 d后处死大鼠,留取大鼠左侧颈总动脉,HE染色后测量各组血管平滑肌肌层厚度及管腔面积,并通过免疫组织化学染色观察p70s6k及TGF-β1的表达情况。结果药物组较损伤组狭窄程度明显减轻[血管平滑肌肌层厚度(0.157±0.016)mm比(0.240±0.022)mm,P<0.05;管腔面积(1.015±0.045)mm2比(0.746±0.050)mm2,P<0.05]。免疫组织化学结果显示,对照组血管平滑肌内p70s6k及TGF-β1无明显表达,损伤组和药物组p70s6k及TGF-β1表达高于对照组(均P<0.05),且药物组p70s6k及TGF-β1表达低于损伤组(P<0.05)。结论依维莫司可以抑制大鼠颈动脉球囊损伤后血管平滑肌细胞的增殖,减少术后再狭窄的发生,其作用机制可能与抑制p70s6k及TGF-β1的表达有关。

【Objective】 To investigate the effect of Everolimus on vascular restenosis in rat models of carotid artery injury.【Methods】 Thirty-six healthy male SD rats were randomly divided into three groups： control group,injury group and medicine group.There were 12 rats in each group.The left common carotid arteries of the injury and medicine group were injured by balloon.The medicine group rats were given Everolimus 1.5 mg/kg one day before operation by gavage,and followed by 0.75 mg/kg per day for 28 days.The rats in control group and injury group were gavaged with same amount of normal saline.All rats were killed at the 28th day and the left common carotid arteries of all cases were taken out.The vascular smooth muscle thickness and lumen area were measured after HE staining.The expression of p70s6k and transforming growth factor-β1（TFG-β1） in arterial wall were detected by immunohistochemistry.【Results】 The vascular stenosis degree in medicine group was significantly lighter than injury group（vascular smooth muscle thickness,（0.157±0.016） mm vs（0.240±0.022） mm,P〈0.05;lumen area,（1.015±0.045） mm^2 vs（0.746±0.050） mm^2,P〈0.05）.The expressions of p70s6k and TFG-β1 were not obvious in vascular smooth muscle cells of control group.The expressions of p70s6k and TFG-β1 in injury group and medicine group were significantly higher than control group（P〈0.05）,and the expressions in medicine group were lower than injury group（P〈0.05）.【Conclusion】 Everrolimus could inhibit the proliferation of vascular smooth muscle cells in rats with injured carotid artery by balloon and reduce the rate of restenosis.The possible mechanism was in connection with inhibition the expression of p70s6k and TFG-β1.