刘华东,熊玮,董少红,吴美善,李江华,张键

• 1:深圳市人民医院心内科暨南大学第二临床医学院
• 2:中国科学院深圳先进技术研究院

摘要(Abstract)：

目的观察抑制趋化素基因对大鼠颈动脉球囊损伤后血管重塑的作用及机制。方法构建大鼠颈动脉球囊损伤模型,模型组只进行球囊损伤术,不进行局部转染;慢病毒对照组球囊损伤术后于颈总动脉局部灌注对照慢病毒30 min;慢病毒抑制组大鼠在球囊损伤术后于颈总动脉局部灌注趋化素基因缺陷慢病毒30 min。在颈动脉局部转染趋化素基因缺陷性慢病毒,转染后第3天采用Real-time PCR检测颈动脉局部组织中趋化素的表达水平。观察抑制趋化素表达后颈动脉的内膜形态变化。采用5-溴-脱氧脲苷(Brd U)法检测颈动脉组织中血管平滑肌细胞的增殖情况,蛋白质免疫印迹法检测颈动脉组织中磷酸化的p38丝裂原活化蛋白激酶(p-p38 MAPK)、磷酸化细胞外调节蛋白激酶(p-ERK 1/2)、磷酸化c-jun氨基末端激酶(p-JNK)的水平。结果在转染趋化素基因缺陷慢病毒后第3天,慢病毒抑制组趋化素mRNA水平显著低于模型组[(0.1633±0.02)比(1.005±0.02),P<0.001],差异有统计学意义。球囊损伤导致大鼠颈动脉内膜Brd U阳性颗粒明显增加,内膜显著增生,p-p38 MAPK、p-ERK 1/2、p-JNK的蛋白水平显著上升;抑制颈动脉中趋化素表达后,大鼠颈动脉内膜Brd U阳性颗粒减少,内膜增生程度减轻,p-p38 MAPK、p-ERK 1/2、p-JNK的蛋白表达水平也随之显著下降。结论趋化素可以通过上调p38 MAPK、ERK 1/2及JNK的磷酸化水平,促进颈动脉损伤后内膜增生的发生。

关键词(KeyWords)： 趋化素;血管平滑肌细胞;血管重塑;丝裂原活化蛋白激酶

Abstract:

Keywords:

基金项目(Foundation): 深圳市科技创新计划项目(jcyj20150403101028192)

作者(Author): 刘华东,熊玮,董少红,吴美善,李江华,张键

参考文献(References)：

• [1]Chistiakov DA,Orekhov AN,Bobryshev YV.Vascular smooth muscle cell inatherosclerosis.Acta Physiol(Oxf),2015,214(1):33-50.
• [2]Goralski KB,Mc Carthy TC,Hanniman EA,et al.Chemerin,a novel adipokine that regulates adipogenesis and adipocyte metabolism.J Biol Chem,2007,282(38):28175-28188.
• [3]Chakaroun R,Raschpichler M,Kl9ting N,et al.Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity.Metabolism,2012,61(5):706-714.
• [4]Wang C,Wu WK,Liu X,et al.Increased serum chemerin level promotes cellular in vasiveness in gastric cancer:a clinical and experimental study.Peptides,2014,51:131-138.
• [5]Stepan H,Philipp A,Roth I,et al.Serum levels ofthe adipokine chemerin are increased In preeclampsia during and 6 months after pregnancy.Regul Pept,2011,168(1-3):69-72.
• [6]Dong B,Ji W,Zhang Y.Elevated serum chemerin levels are associated with the presence of coronary artery disease in patients with metabolic syndrome.Intern Med,2011,50(10):1093-1097.
• [7]Zhang O,Ji Q,Lin Y,et al.Circulating chemerin levels elevated in dilated cardiomyopathy patients with overt heart failure.Clin Chim Acta,2015,448:27-32.
• [8]熊玮,董少红,张键,等.Chn1基因缺陷性小鼠血管平滑肌细胞株的构建和鉴定.广东医学,2015,36(16):2495-2498.
• [9]熊玮,董少红,张键,等.趋化素通过上调磷酸化JNK促进小鼠血管平滑肌细胞的增殖.中国病理生理杂志,2015,31(12):2282-2286.
• [10]Liu H,Dong S,Xiong W,et al.Effects of high mobility group box 1 and nuclear factorκB on neointimal hyperplasia after common carotid artery balloon injury.Int J Clin Exp Med,2015,8(8):13323-13328.
• [11]Mattern A,Zellmann T,Beck-Sickinger AG.Processing,signaling,and physiological function of Chemerin.IUBMB Life,2014,66(1):19-26.
• [12]Herenius MM,Oliveira AS,Wijbrandts CA,et al.Anti-TNF therapy reduces serum levels of chemerin in rheumatoid arthritis:a new mechanism by which anti-TNF might reduce inflammation.PLo S One,2013,8(2):e57802.
• [13]Dessein PH,Tsang L,Woodiwiss AJ,et al.Circulating concentrations of the novel adipokine chemerin are associated with cardiovascular disease risk in rheumatoid arthritis.J Rheumatol,2014,41(9):1746-1754.
• [14]Kaur J,Adya R,Tan BK,et al.Identification of chemerin receptor(ChemR23)in human endothelial cells:chemerininduced endothelial angiogenesis.Biochem Biophys Res Commun,2010,391(4):1762-1768.
• [15]Watts SW,Dorrance AM,Penfold ME,et al.Chemerin connects fat to arterial contraction.Arterioscler Thromb Vasc Biol,2013,33(6):1320-1328.
• [16]Davis-Dusenbery BN,Wu C,Hata A.Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation.Arterioscler Thromb Vasc Biol,2011,31(11):2370-2377.