低剪应力对兔颈动脉粥样硬化进展的影响
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摘要
目的通过兔颈动脉低剪应力(low shear stress,LSS)动物模型,探讨低剪应力对兔颈动脉粥样硬化进展的影响。方法雄性新西兰大白兔16只分为2个组:假手术组(对照组)及颈动脉缩窄组(LSS组),每组各8只。通过左侧颈动脉缩窄手术建立兔颈动脉LSS动物模型;每隔两周行兔颈动脉超声检测颈动脉内径(inner diameter,D)、内中膜厚度(internal-media thickness,IMT)、收缩期峰值流速(peak systolic velocity,PSV)及血流阻力指数(resistive index,RI),应用剪应力(wall shear stress,WSS)定量分析软件分析兔颈动脉剪应力空间分布情况;术后8周处死所有家兔,取颈动脉制成病理切片观察颈动脉病变的形态特征。结果与术前比较,对照组术后4、8周兔颈动脉D、IMT、PSV及RI均无明显差异(P>0. 05);与对照组比较,LSS组术后4周、术后8周兔颈动脉D、PSV及RI均呈现明显减低,术后8周出现IMT增加(P<0. 05);超声检查见LSS组兔颈动脉血流呈低阻低排改变。各时间点正常兔颈动脉血流WSS分布在4～10 dyne/cm~2(占78. 6%),颈动脉血流WSS均值为(6. 05±1. 19) dyne/cm~2;而LSS组兔颈动脉血流WSS分布呈现普遍减低,分布在2～6 dyne/cm~2(占81. 3%),颈动脉血流WSS均值为(2. 96±0. 79) dyne/cm~2。兔颈总动脉病理切片中,LSS组中兔左侧颈总动脉出现不同程度的内-中膜不规则增厚、脂质沉积增加,甚至出现纤维帽形成及动脉粥样硬化斑块形成,而对照组的兔颈总动脉均为正常。结论 LSS刺激能够诱导兔颈总动脉内中膜增厚及脂质沉积,LSS在兔颈动脉粥样硬化的形成中具有重要作用。
Objective To explore the impact of low shear stress( LSS) on the formation of carotid atherosclerosis by establishing LSS model of rabbit in vivo. Methods Sixteen New Zealand white male rabbits were randomly divided into the control group( n = 8) and LSS group( n = 8),the LSS model was induced by left carotid artery constriction surgery,and the sham surgery was performed in control group.The carotid ultrasound examination was performed every two weeks after surgery. The inner diameter( D),internal-media thickness( IMT),peak systolic velocity( PSV) and flow resistive index( RI) of left carotid artery were measured and the spatial distribution of the wall shear stress( WSS) was determined by WSS quantitative analysis software. All animals were sacrificed in the 8th week and the morphology of carotid artery lesions was observed by pathological examination. Results There was no significant difference in D,IMT,PSV and RI in control group before and 4 or 8 week after operation( P>0. 05). Compared with the control group,the D,PSV and RI decreased significantly in LSS group at the 4th and 8th week after operation while the IMT increased at the 8th week( P < 0. 05). In control group,the value distribution of WSS in left common carotid artery ranged 4-10 dyne/cm~2( 78. 6%) with a mean value of( 6. 05±1. 19) dyne/cm~2; while in LSS group,the value distribution of WSS widely reduced,ranging 2-6dyne/cm~2( 81. 3%) with a mean value of( 2. 96±0. 79) dyne/cm~2. Through dynamical pathological examination, the intimal thickening, the lipid deposition, the fibrous cap formation as well as atherosclerotic plaques were observed only in LSS group. Conclusion LSS may stimulate and induce the intimal thickening and lipid deposition in the carotid artery,leading to the formation of carotid atherosclerosis in rabbits.
Objective To explore the impact of low shear stress( LSS) on the formation of carotid atherosclerosis by establishing LSS model of rabbit in vivo. Methods Sixteen New Zealand white male rabbits were randomly divided into the control group( n = 8) and LSS group( n = 8),the LSS model was induced by left carotid artery constriction surgery,and the sham surgery was performed in control group.The carotid ultrasound examination was performed every two weeks after surgery. The inner diameter( D),internal-media thickness( IMT),peak systolic velocity( PSV) and flow resistive index( RI) of left carotid artery were measured and the spatial distribution of the wall shear stress( WSS) was determined by WSS quantitative analysis software. All animals were sacrificed in the 8th week and the morphology of carotid artery lesions was observed by pathological examination. Results There was no significant difference in D,IMT,PSV and RI in control group before and 4 or 8 week after operation( P>0. 05). Compared with the control group,the D,PSV and RI decreased significantly in LSS group at the 4th and 8th week after operation while the IMT increased at the 8th week( P < 0. 05). In control group,the value distribution of WSS in left common carotid artery ranged 4-10 dyne/cm~2( 78. 6%) with a mean value of( 6. 05±1. 19) dyne/cm~2; while in LSS group,the value distribution of WSS widely reduced,ranging 2-6dyne/cm~2( 81. 3%) with a mean value of( 2. 96±0. 79) dyne/cm~2. Through dynamical pathological examination, the intimal thickening, the lipid deposition, the fibrous cap formation as well as atherosclerotic plaques were observed only in LSS group. Conclusion LSS may stimulate and induce the intimal thickening and lipid deposition in the carotid artery,leading to the formation of carotid atherosclerosis in rabbits.
引文
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[24]刘加春,王大明,李雅国,等.小型猪颈动脉粥样硬化性狭窄模型的初步建立[J].中华神经外科杂志,2006,22(12):756-758.
[25]刘华,王贵学,叶林奇,等.一种可控的切应力及LDL浓度极化动物模型的建立及对动脉粥样硬化的影响[J].第三军医大学学报,2009,31(20):1981-1985.
[26]ISHII A,VI UELA F,MURAYAMA Y,et al.Swine model of carotid artery atherosclerosis:experimental induction by surgical partial ligation and dietary hypercholesterolemia[J].Ajnr Am J Neuroradiol,2006,27(9):1893-1899.
[2]SAMADY H,ESHTEHARDI P,MCDANIEL M C,et al.Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease[J].Circulation,2011,124(7):779-788.
[3]FRY D L.Acute vascular endothelial changes associated with increased blood velocity gradients[J].Circ Res,1968,22(2):165-197.
[4]CG C,JM F G,RC S.Arterial wall shear and distribution of early atheroma in man[J].Nature,1969,223(5211):1159-1160.
[5]吴孟津,危当恒,王贵学,等.低剪切应力促进基质细胞衍生因子1在动脉粥样硬化斑块中表达[J].中国动脉硬化杂志,2006,14(12):1028-1030.
[6]刘少飞,匡雅姝,彭盛,等.单核细胞来源的微颗粒通过PPAR-α-SR-BI途径促进RAW264.7泡沫细胞形成的研究[J].同济大学学报(医学版),2017,38(4):6-12.
[7]PEIFFER V,SHERWIN S J,WEINBERG P D.Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis?A systematic review[J].Cardiovasc Res,2013,99(2):242-250.
[8]TIMMINS L H,MACKIE B D,OSHINSKI J N,et al.Colocalization of low and oscillatory coronary wall shear stress with subsequent culprit lesion resulting in myocardial infarction in an orthotopic heart transplant patient[J].JACC Cardiovasc Interv,2013,6(11):1210-1211.
[9]WENTZEL J J,CHATZIZISIS Y S,GIJSEN F J,et al.Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling:current understanding and remaining questions[J].Cardiovasc Res,2012,96(2):234-243.
[10]CHISTIAKOV D A,OREKHOV A N,BOBRYSHEV YV.Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology[J].Exp Mol Pathol,2016,100(3):409-415.
[11]TZIMA E,IRANITEHRANI M,KIOSSES W B,et al.A mechanosensory complex that mediates the endothelial cell response to fluid shear stress[J].Nature,2005,437(7057):426-431.
[12]WANG C H,CHEN M,LIU S L,et al.Spatial distribution of wall shear stress in common carotid artery by color doppler flow imaging[J].J Digit Imaging,2013,26(3):466-471.
[13]OULAID O,ZHANG J.Temporal and spatial variations of wall shear stress in the entrance region of microvessels[J].J Biomech Eng,2015,137(6):061008.
[14]SS D,RP A N,JR B,et al.Shear stress and plaque development[J].Expert Rev Cardiovasc Ther,2010,8(4):545-556.
[15]SATO M,OHSHIMA N.Flow-induced changes in shape and cytoskeletal structure of vascular endothelial cells[J].Biorheology,1994,31(2):143-153.
[16]王克强.动脉粥样硬化形成中血流切应力对血管内皮细胞影响的研究进展[J].解剖科学进展,1997,(3):6-12.
[17]NEREM R M,LEVESQUE M J,CORNHILL J F.Vascular Endothelial Morphology as an Indicator of the pattern of blood flow[J].J Biomech Eng,1981,103(3):172-176.
[18]DEWEY C F Jr,BUSSOLARI S R,GIMBRONE M A JR,et al.The dynamic response of vascular endothelial cells to fluid shear stress[J].J Biomecha Eng,1981,103(3):177-185.
[19]MCNALLY J S,DAVIS M E,GIDDENS D P,et al.Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress[J].Am J Physiol Heart Circ Physiol,2003,285(6):H2290-2297.
[20]WALPOLA P L,GOTLIEB A I,CYBULSKY M I,et al.Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress[J].Arterioscler Thromb Vasc Biol,1995,15(1):2-10.
[21]CHENG C,TEMPEL D,VAN HAPEREN R,et al.Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress[J].Circulation,2006,113(23):2744-2253.
[22]KIM V B,BROWN P M,BROWN P M JR,et al.A carotid stenosis model in canines[J].J Invest Surge,2001,14(4):241-247.
[23]DURAND E,MALLAT Z,ADDAD F,et al.Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model[J].J Am Coll Cardiol,2002,39(10):1680-1685.
[24]刘加春,王大明,李雅国,等.小型猪颈动脉粥样硬化性狭窄模型的初步建立[J].中华神经外科杂志,2006,22(12):756-758.
[25]刘华,王贵学,叶林奇,等.一种可控的切应力及LDL浓度极化动物模型的建立及对动脉粥样硬化的影响[J].第三军医大学学报,2009,31(20):1981-1985.
[26]ISHII A,VI UELA F,MURAYAMA Y,et al.Swine model of carotid artery atherosclerosis:experimental induction by surgical partial ligation and dietary hypercholesterolemia[J].Ajnr Am J Neuroradiol,2006,27(9):1893-1899.