Toll样受体4—核因子κB信号通路在血管成形术后再狭窄过程中的作用  

Toll Like Receptor 4/ Nuclear Factor-KappaB Pathway Play a Potent Role in the Restenosis

作　　者：马林[1] 丁彦春[1] 崔晓琼[1] 姜华[1] 王虹艳[1] 曲鹏[1] 

机构地区：[1]大连医科大学附属第二医院心内科,辽宁省大连市116023

出　　处：《中国动脉硬化杂志》2006年第7期596-600,共5页Chinese Journal of Arteriosclerosis

摘　　要：目的观察大鼠颈总动脉球囊损伤术后血管中Toll样受体4及核因子κB的表达情况,并应用阿托伐他汀药物进行干预。探讨Toll样受体4/核因子κB通路在再狭窄过程中的作用。方法雄性SD大鼠56只,随机分为阿托伐他汀治疗7天组、内膜损伤7天组、阿托伐他汀治疗14天组、内膜损伤14天组,以同系动物的右颈总动脉作对照。采用大鼠颈总动脉球囊损伤后再狭窄动物模型,以免疫组织化学染色、逆转录聚合酶链反应、Western blot法检测Toll样受体4及核因子κB在各组大鼠颈总动脉中的表达情况。结果大鼠颈总动脉球囊损伤后7天新生内膜增加,在新生内膜平滑肌中核因子κB(9.8%)及Toll样受体4(15.6%)染色阳性,Toll样受体4 mRNA(0.39)及蛋白水平(26.18)均增高。14天后内膜增生更加明显,管腔显著狭窄,核因子κB(23.2%)及Toll样受体4(37.2%)染色强阳性,Toll样受体4 mRNA(0.49)及蛋白水平(57.12)显著增高。与内膜损伤组相比,阿托伐他汀治疗组内膜增生程度明显减轻,核因子κB及Toll样受体4水平明显下降。结论在大鼠颈总动脉球囊损伤后再狭窄模型中,核因子κB活性增加,Toll样受体4 mRNA及蛋白水平均增高,应用阿托伐他汀后可以抑制Toll样受体4和核因子κB的表达,同时抑制内膜增生,表明Toll样受体4/核因子κB通路有可能参与了再狭窄形成过程。Aim To observe the expression of Tolllike receptor4 （TLR4） and nuclear factor-kappaB （NF-κB） inthe model of vascular restenosis established by balloon injury, and the effects of atorvastatin on neoitmal proliferation and expression of TLR4 and NF-κB. To explore a possible role for TLR4/NF-κB pathway in the developing of restenosis. Methods 56 male Sprague-Dawley rats were randomly divided into 5 groups： atorvastatin treatment 1 week group, balloon injury 1 week group, atorvastatin treatment 2 weeks group, balloon injury 2 weeks group, and control group. Balloon catheter denudation of the endothelium in the common carotid artery of the rat was routinely used as a model of restenosis. Immunohistochemistry and reverse transcription-polymerase chain reaction （RT-PCR）, Western blot were used to detect the the expression of TLR4 and NF-κB on rat carotid arteries at different groups. Results The proliferation of vascular smooth muscle cell （VSMC） existed on the surface of vascular lttmen on 1 week after endothelium denudation. TLR4 （ 15.6% ） and NF-κB （9.8%） were stained on SMC of neointimal. The levels of TLR4 rnRNA （0.39） andprotein （ 26 .18 ） of earotid arteries were inereased eompared with those of the control group. After 2 weeks, the neointimal were significandy hyperplasia, the lumen were striking stenosis, hnmunestain of TLR4 （37.2%） and NF-κB （23.2%） were mostly positive in the neointimal cells. The level of TLR4 mRNA （0.49） and protein （57.12） of carotid arteries were significantly increased. Treatment of rats with the atorvastatin caused a significant inhibition of the expression of TLR4 and NF-κB as well as neointima form （ P 〈 0.05 ）. Conclusion In the model of vascular restenosis by balloon injury, the levels of TLR4 rnRNA and protein of carotid arteries were significandy increased and companied with activation of NF-κB. Treatment of rats with the atorvastatin caused a significant inhibition of the expression of TLR4 and NF-κB as well as neoi

关 键 词：内科学 再狭窄 大鼠 阿托伐他汀 炎症 TOLL样受体4 核因子ΚB 

分 类 号：R5[医药卫生—内科学]