阿托伐他汀减轻大鼠颈动脉损伤后组织蛋白酶S表达的影响

Atorvastatin Attenuated Cathepsin S Expression in Neointima after Carotid Artery Balloon Injury in Rats

背景新生内膜形成是动脉粥样硬化、再狭窄等血管病理改变时的重要特征。阿托伐他汀能否通过抑制参与血管生成的组织蛋白酶S(Cathepsin S, Cat S)及核转录因子κB(NF-κB)表达减轻新生内膜形成目前尚不清楚。目的观察阿托伐他汀对大鼠颈动脉球囊损伤后Cat S及NF-κB表达的影响。方法 24只雄性SD大鼠分为正常对照组(n=8)、手术组(n=8)和阿托伐他汀组(n=8) ,手术组和阿托伐他汀组行左侧颈动脉球囊损伤。阿托伐他汀组予阿托伐他汀10 mg/(kg.d)。实验前后测定血清白细胞介素1β(IL-1β)变化,28 d后大鼠处死行病理形态学检查,检测各组Cat S和NF-κB表达。结果与手术组比较,阿托伐他汀组大鼠颈动脉内膜面积和内膜/中膜面积(I/ M)比值明显减少[内膜面积:(148.6±8.8)×103比(64.8±5.1)×103μm2;I/ M:(2.1±0.2)比(0.9±0.1) ,均P<0.01]。与手术组比较,阿托伐他汀组Cat S表达和NF-κB评分也明显减少[Cat S mRNA:(0.80±0.07)比(0.50±0.04) ;Cat S评分:(15.3±1.4)比(8.5±0.7) ;NF-κB评分:(12.5±1.3)比(6.7±0.5) ,均P<0.01]。内膜面积与Cat S和NF-κB表达呈正相关(P<0.05)。结论阿托伐他汀可能通过抑制NF-κB使Cat S表达减少,减轻颈动脉球囊损伤后新生内膜形成。

Background Neointima formation plays an important role in the pathogenesis of atherosclerosis and restenosis after angioplasty. We hypothesized if atorvastatin inhibits neointima formation mediating decrea- ses in cathepsin S （Cat S） and nuclear factor-κB（NF-κB） expression. Objective The study was aimed to explore the effect of atorvastatin on the neointima formation, Cat S and NF-κB expression in rats after balloon-injured carotid artery. Methods Twenty four male Sprague-Dawley rats were randomly one of three arms., control group （n=8）, surgery group（n=8） and atorvastatin group [10 mg/（kg . d）, n=8] for 4 weeks. Surgery and atorvastatin group were performed with balloon angioplasty to the left common carotid artery. The serum levels of IL-κB were measured using enzyme-link-immunosorbent assay（ELISA）. Carotid arteries were excised and examined with pathomorphology. The expression of Cat S and NF-κB was measured using using the RT-PCR and immunohistochemistry techniques. Results Compared with surgery group, atorvastatin decreased intima area and intima media ratio（I/M）Eintima area= （148.6±8.8））〈10^3 vs （64.8±5.1） ×10^3μm2 ; I/M：（2. 1±0.2） vs （0.9±0.1）, all P〈0. 01]. Atorvastatin commensurately decreased the expression of Cat S and NF-nB [Cat S mRNA： （0.80±0.07） vs （0.50±0.04） ; Cat S score： （15.3±1.4） vs （8.5±0.7） ; NF-κB score：（12.5±1.3） vs （6.7± 0.5）, all P〈0.01]. The intima area was significantly positively correlated with the Cat S and NF-κB expression （all P〈0.05）. Conclusion Atorvastatin attenuates the neointima formation which was associated with decreases in Cat S expression and inhibition of NF-κB.