【作者】 龚凡；

【导师】 曾秋棠；

【作者基本信息】 华中科技大学 ， 内科学， 2010， 硕士

【摘要】 目的:研究阿托伐他汀对颈动脉球囊损伤大鼠核孤儿受体Nur77表达的影响及其与血管平滑肌细胞(VSMCs)增殖的关系,探讨阿托伐他汀防治血管球囊损伤术后再狭窄(RS)新的作用机制。方法:120只清洁级SD大鼠(体重300-350克)随机分为空白对照组(假手术组)(BCG)10只、控制组(颈动脉球囊损伤组)(CG)55只和颈动脉球囊损伤+阿托伐他汀干预组(AIG)55只。于术后7、14、21、28d取材,病理形态学分析比较各组血管内膜-中膜厚度比及平滑肌细胞增殖率;应用免疫组织化学法及Western Blot分析各组血管组织中Nur77蛋白的表达;RT-PCR检测各组血管组织中ERK、PDGF-B、Nur77、NF-κB的基因表达。结果:与空白对照组(假手术组)(BCG)相比较控制组(颈动脉球囊损伤组)(CG)中Nur77蛋白表达水平明显增高,血管内膜-中膜显著增厚(P<0.01);控制组(颈动脉球囊损伤组)(CG)与颈动脉球囊损伤+阿托伐他汀干预组(AIG)相比较Nur77蛋白表达水平降低,血管内膜-中膜厚度比变薄(P<0.05)。结论:血管球囊损伤术后,鼠颈动脉内膜增厚, Nur77高表达,血管平滑肌细胞增殖;阿托伐他汀降低损伤血管Nur77表达,抑制血管平滑肌细胞的增殖。通过降低Nur77表达抑制VSMCs增殖,可能是他汀类药物新的预防血管损伤术后再狭窄的机制。更多还原

【Abstract】 Objective: To investigate the effects of atorvastatin on the expression of Nur77 in vas cular smooth muscle cells (VSMCs ) of rat carotid artery postangioplasty restenosis models which were established , and to explore the relationship between Nur77 and VSMCs proliferation and new mechanism which atorvastatin prevented restenosis of blood vessel after balloon-injury.Methods: 120 clean-class male Sprague Dawley rats (weight 300-350g) were randomly divided into three groups. Labeled: blank control group (sham-operated group ) (BCG) 10 rats, control group (carotid artery balloon- injury group ) (CG) 55 rats, and carotid artery balloon- injury + atorvastatin intervention group (AIG) 55 rats. The arteries were harvested on day 7, 14, 21, 28 after balloon-injury. Analysis and comparison the ratio of intima to media thickness and lumen area were assessed by pathomorphology.β-SMA、Nur77 and PCNA expression were assessed by immunohistochemistry; PDGF-B、Nur77、ERK、NF-κB expression were assessed by real-time PCR (RT-PCR); Nur77 expression was assessed by Western Blot. Result: Nur77 expression levels and the ratios of intima to media thickness and lumen area of carotid artery balloon- injury group were higher compared with blank control group (BCG); Nur77 expression levels and the ratio of intima to media thickness and lumen area of carotid artery balloon- injury + atorvastatin intervention group (AIG) were lower compared with control group (CG).Conclusion: After carotid artery balloon-injury in rats, compared with before it , thickness of intima of carotid artery were higher, Nur77 expression levels of vascular smooth muscle were higher, and proliferation of VSMCs were significantly almost at the same time . Atorvastatin inhibited VSMCs proliferation by regulating nuclear orphan receptor nur77 expression. By reducing the Nur77 expression in VSMCs proliferation, statins prevented new vascular damage mechanism of postoperative restenosis.更多还原