冠状动脉粥样斑块内CD45表达水平与病灶结构变化的关系
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摘要
目的通过检测冠状动脉粥样硬化病灶内CD45蛋白表达水平,分析其与病灶结构变化的关系,探讨CD45在人冠状动脉粥样硬化病灶发生发展中的作用。方法收集贵州医科大学法医司法鉴定中心司法鉴定中尸体检验及组织学检查确认有冠状动脉粥样硬化病例的冠状动脉组织,根据冠状动脉病变情况将其分为对照组、单纯动脉粥样硬化组(单纯As组)和动脉粥样硬化并继发病变组(As并继发病变组),常规石蜡切片HE染色观察各组冠状动脉的组织结构,免疫组织化学染色法、蛋白免疫印迹法及实时荧光定量PCR检测CD45蛋白的表达分布及水平,分析CD45表达水平与粥样硬化病灶结构变化的关系。结果与对照组比较,有动脉粥样硬化及并发继发病变的冠状动脉斑块内纤维帽厚度变薄,病灶厚度、坏死灶厚度及血管腔面积增加(P均<0.05)。与对照组比较,有动脉粥样硬化及并发继发病变的血管组织CD45蛋白表达显著升高(P<0.05),且As并继发病变组显著高于单纯As组(P<0.05)。与对照组比较,有动脉粥样硬化及发生继发病变的冠状动脉病灶内CD45的表达显著升高(P<0.05),且As并继发病变组显著高于单纯As组(P<0.05),CD45阳性蛋白表达主要分布于斑块肩部和底部的白细胞(棕黄色着色)。与对照组比较,有动脉粥样硬化及并发继发病变的血管组织CD45 mRNA表达显著升高(P<0.05),且As并继发病变组显著高于单纯As组(P<0.05)。病灶内CD45表达水平与病灶结构变化具有相关性。结论人冠状动脉粥样斑块内CD45分子作为炎症反应的标志物,其表达水平反映病灶内的炎症反应程度,而病灶内炎症反应程度能影响病灶结构,从而导致斑块稳定性改变。
Aim By examining the level of CD45 protein expression in coronary atherosclerotic lesions,and to analyze the relationship between CD45 and lesions structure changes and explore the role of CD45 in the development of coronary atherosclerotic lesions in humans. Methods Specimens of coronary arteries were obtained from Forensic Judicial Expertise Center,Guizhou Medcial University with coronary atherosclerosis. The coronary arteries were classified into three groups according to the lesions: control,atherosclerosis,atherosclerosis and secondary lesion. Routine HE staining of paraffin sections was performed to observe the histological structure of coronary artery in the three groups. The expression level of CD45 protein was detected by immunohistochemical staining,Western blot and Real-time PCR. The relationship between the expression of CD45 and the structural changes of atherosclerotic lesions were analyzed. Results( 1)Compared with the control group,the thickness of the fibrous cap in the coronary arterial plaque with atherosclerosis and secondary lesions became thinner,and the thickness of the lesion,the thickness of the necrosis lesion,and the lumen area of the vessel increased( P<0.05).( 2) There was a statistically significant difference in the expression of CD45 protein between vascular tissues.( 3) There was a statistically significant difference in the expression of CD45 between the control group,the atherosclerosis group and the secondary lesions,and it was mainly expressed in the all leukocytes of the plaques shoulder and bottom.( 4) There was a statistically significant difference in the expression of CD45 mRNA between three groups.( 5) CD45 expression was related to lesion structure changes. Conclusion The level of CD45 expression reflects the extent of inflammation in human coronary atherosclerotic plaque,and the extent of inflammation within the lesion can affect the structure of the lesion.
Aim By examining the level of CD45 protein expression in coronary atherosclerotic lesions,and to analyze the relationship between CD45 and lesions structure changes and explore the role of CD45 in the development of coronary atherosclerotic lesions in humans. Methods Specimens of coronary arteries were obtained from Forensic Judicial Expertise Center,Guizhou Medcial University with coronary atherosclerosis. The coronary arteries were classified into three groups according to the lesions: control,atherosclerosis,atherosclerosis and secondary lesion. Routine HE staining of paraffin sections was performed to observe the histological structure of coronary artery in the three groups. The expression level of CD45 protein was detected by immunohistochemical staining,Western blot and Real-time PCR. The relationship between the expression of CD45 and the structural changes of atherosclerotic lesions were analyzed. Results( 1)Compared with the control group,the thickness of the fibrous cap in the coronary arterial plaque with atherosclerosis and secondary lesions became thinner,and the thickness of the lesion,the thickness of the necrosis lesion,and the lumen area of the vessel increased( P<0.05).( 2) There was a statistically significant difference in the expression of CD45 protein between vascular tissues.( 3) There was a statistically significant difference in the expression of CD45 between the control group,the atherosclerosis group and the secondary lesions,and it was mainly expressed in the all leukocytes of the plaques shoulder and bottom.( 4) There was a statistically significant difference in the expression of CD45 mRNA between three groups.( 5) CD45 expression was related to lesion structure changes. Conclusion The level of CD45 expression reflects the extent of inflammation in human coronary atherosclerotic plaque,and the extent of inflammation within the lesion can affect the structure of the lesion.
引文
[1]邢聪慧,管军,王旭,等.心绞痛患者冠脉内斑块组织虚拟性血管内超声影像学特征及与炎症因子的关系[J].中国超声医学杂志,2010,26(10):912-914.
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[11]Libby P. Inflammation in atherosclerosis[J]. J Assoc Physicians India,2002,48(2):265-266.
[12]Vitiello L,Spoletini I,Gorini S,et al. Microvascular inflammation in atherosclerosis[J]. Ijc Metabolic Endocrine,2014,3(C):1-7.
[13]Eriksson E E,Xie X,Werr J,et al. Direct viewing of atherosclerosis in vivo:plaque invasion by leukocytes is initiated by the endothelial selectins[J]. FASEB J,2001,15(7):1149-1157.
[14]左海奇,李碧澄.中性粒细胞胞外陷阱网在动脉粥样硬化进展中的作用[J].中国动脉硬化杂志,2017,25(6):635-639.
[15]Flores-Borja F,Kabouridis P S,Jury E C,et al. Altered lipid raft-associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus[J]. Arthritis Rheum,2010,56(1):291-302.
[16]Hennig B J,Fry A E,Hirai K,et al. PTPRC(CD45)variation and disease association studied using single nucleotide polymorphism tagging[J]. Tissue Antigens,2008,71(5):458-463.
[17]LecewicztoruńB,Pietrzak A,Roliński J,et al. The peripheral blood lymphocyte pattern in psoriasis preceded by an infection[J]. Med Sci Monit,2001,7(5):889.
[18]张艳敏,雷春莲,成革胜,等. RSV感染患儿外周血CD4 CD45RO+CD45RA+表达变化的研究[J].中国当代儿科杂志,2001,3(3):260-261.
[19] Robichaud G A,Barbeau B,Fortin J F,et al. Nuclear factor of activated T cells is a driving force for preferential productive HIV-1 infection of CD45RO-expressing CD4+T cells[J]. J Biol Chem,2002,277(26):23733-23741.
[20]杨银洁.内皮祖细胞亚群与颅内外脑动脉粥样硬化症严重程度的相关性研究[J].神经损伤与功能重建,2016,11(5):388-389.
[21]臧璇.亲环素A在动脉粥样硬化斑块中表达的临床研究[D].江苏大学,2013.
[22]李克雷,薛婧,魏强. CD45分子在HIV-1病毒感染中的作用研究进展[J].中国比较医学杂志,2017,27(6):82-85.
[23]方顺淼.动脉粥样硬化破裂斑块模型的创建及骨髓干细胞动员与移植对破裂斑块修复的研究[D].南方医科大学,2009.
[24]韦立新,唐庆贺,孙璐,等.人体冠状动脉粥样硬化斑块中氧化低密度脂蛋白和新生血管与斑块稳定性的关系[J].中华病理学杂志,2006,35(3):138-141.
[25]肖学慧,刘艳阳,张越.血清炎性细胞及炎性因子与冠心病斑块稳定性相关性研究现状[J].医学综述,2015(12):2115-2117.
[26]石怀银,韦立新,佘铭鹏,等.冠状动脉斑块中炎性细胞和平滑肌细胞的定量及其与斑块稳定性的关系[J].中华病理学杂志,1999,28(4):256-259.
[2]Davies M J. Stability and instability:two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995[J].Circulation,1996,94(8):2013-2020.
[3]耿俊梅,万昌武,乐翠云,等.人冠状动脉粥样硬化病灶内CD40L水平与病灶结构变化的关系[J].中国动脉硬化杂志,2017,25(4):355-359.
[4]廖思聪,于杨,王大新,等.动脉粥样硬化中巨噬细胞介导胞葬作用的研究进展[J].中国动脉硬化杂志,2018,26(2):201-206.
[5]Penninger J M,Irie-Sasaki J,Sasaki T,et al. CD45:new jobs for an old acquaintance[J]. Nat Immunol,2001,2(5):389-396.
[6]Dawes R,Petrova S,Liu Z,et al. Combinations of CD45isoforms are crucial for immune function and disease[J]. J Immunol,2006,176(6):3417.
[7]Jury E C,Kabouridis P S,Floresborja F,et al. Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus[J]. J Clin Invest,2004,113(8):1176-1187.
[8]Raffel O C,Tearney G J,Gauthier D D,et al. Relationship between a systemic inflammatory marker,plaque inflammation,and plaque characteristics determined by intravascular optical coherence tomography[J]. Arterioscler Thromb Vasc Biol,2007,27(8):1820.
[9] Hansson G K,Robertson A K,Sōderberg-Nauclér C. Inflammation and atherosclerosis[J]. Annu Rev Pathol,2006,31(4):297-329.
[10]陈文强,张运.动脉粥样硬化易损斑块的动物模型和检测技术[J].中国动脉硬化杂志,2016,24(7):649-656.
[11]Libby P. Inflammation in atherosclerosis[J]. J Assoc Physicians India,2002,48(2):265-266.
[12]Vitiello L,Spoletini I,Gorini S,et al. Microvascular inflammation in atherosclerosis[J]. Ijc Metabolic Endocrine,2014,3(C):1-7.
[13]Eriksson E E,Xie X,Werr J,et al. Direct viewing of atherosclerosis in vivo:plaque invasion by leukocytes is initiated by the endothelial selectins[J]. FASEB J,2001,15(7):1149-1157.
[14]左海奇,李碧澄.中性粒细胞胞外陷阱网在动脉粥样硬化进展中的作用[J].中国动脉硬化杂志,2017,25(6):635-639.
[15]Flores-Borja F,Kabouridis P S,Jury E C,et al. Altered lipid raft-associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus[J]. Arthritis Rheum,2010,56(1):291-302.
[16]Hennig B J,Fry A E,Hirai K,et al. PTPRC(CD45)variation and disease association studied using single nucleotide polymorphism tagging[J]. Tissue Antigens,2008,71(5):458-463.
[17]LecewicztoruńB,Pietrzak A,Roliński J,et al. The peripheral blood lymphocyte pattern in psoriasis preceded by an infection[J]. Med Sci Monit,2001,7(5):889.
[18]张艳敏,雷春莲,成革胜,等. RSV感染患儿外周血CD4 CD45RO+CD45RA+表达变化的研究[J].中国当代儿科杂志,2001,3(3):260-261.
[19] Robichaud G A,Barbeau B,Fortin J F,et al. Nuclear factor of activated T cells is a driving force for preferential productive HIV-1 infection of CD45RO-expressing CD4+T cells[J]. J Biol Chem,2002,277(26):23733-23741.
[20]杨银洁.内皮祖细胞亚群与颅内外脑动脉粥样硬化症严重程度的相关性研究[J].神经损伤与功能重建,2016,11(5):388-389.
[21]臧璇.亲环素A在动脉粥样硬化斑块中表达的临床研究[D].江苏大学,2013.
[22]李克雷,薛婧,魏强. CD45分子在HIV-1病毒感染中的作用研究进展[J].中国比较医学杂志,2017,27(6):82-85.
[23]方顺淼.动脉粥样硬化破裂斑块模型的创建及骨髓干细胞动员与移植对破裂斑块修复的研究[D].南方医科大学,2009.
[24]韦立新,唐庆贺,孙璐,等.人体冠状动脉粥样硬化斑块中氧化低密度脂蛋白和新生血管与斑块稳定性的关系[J].中华病理学杂志,2006,35(3):138-141.
[25]肖学慧,刘艳阳,张越.血清炎性细胞及炎性因子与冠心病斑块稳定性相关性研究现状[J].医学综述,2015(12):2115-2117.
[26]石怀银,韦立新,佘铭鹏,等.冠状动脉斑块中炎性细胞和平滑肌细胞的定量及其与斑块稳定性的关系[J].中华病理学杂志,1999,28(4):256-259.