黄孝宇

• 1:河南省第二人民医院病理科

摘要(Abstract)：

目的研究单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)及核转录因子-kappa(NF-KB)在人颅内动脉瘤中的水平表达。方法选取30例颅动脉瘤标本和12例正常颅动脉标本,分为颅动脉瘤组和对照组;免疫组化方法检测颅动脉瘤组和对照组中ICAM-1、NF-KB阳性表达,并且计算MD值;蛋白质免疫印迹法(Western-blot)法检测2组MCP-1蛋白表达,计算2组中的含量水平。结果免疫组化结果发现,ICAM-1、NF-KB两种蛋白在颅动脉瘤组均有明显表达,阳性反应较为明显,且MD值分别达到了(0.294±0.035)、(0.354±0.025),而正常颅动脉组中的ICAM-1、NF-B显示了较微弱的阳性反应,且平均光密度(Mean Density,MD)值分别仅为(0.083±0.020)、(0.092±0.041),相比之下,存在显著性的差异(P<0.05);Western-blot法检测结果显示,颅动脉瘤组标本中MCP-1蛋白表达明显较正常颅动脉组多,MCP-1值为(1.80±0.25),而正常颅动脉组为(0.30±0.32),差异有统计学意义(P<0.05)。结论 MCP-1、ICAM-1和NF-KB三种蛋白在颅动脉瘤中有着较高的表达,推测可导致IA的形成以及破裂,为临床诊断提供一定的依据。

关键词(KeyWords)： 颅内动脉瘤;单核细胞趋化因子-1;细胞间黏附因子-1;核转录因子-kappa;免疫组化;蛋白质免疫印迹

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 黄孝宇

参考文献(References)：

• [1] 徐东宝,李小龙,李健,等.颅内动脉瘤的血流动力学研究进展[J].中华临床医师杂志,2013,7(19):8 843-8 844.
• [2] DHANDAPANI S,SINGH A,SINGLA N,et al.Has Outcome of Subarachnoid Hemorrhage Changed With Improvements in Neurosurgical Services[J].Stroke,2018,49(12):2 890-2 895.
• [3] LA PIRA B,SINGH TD,RABINSTEIN AA,et al.Time Trends in Outcomes After Aneurysmal Subarachnoid Hemorrhage Over the Past 30 Years[J].Mayo Clin Proc,2018 Dec;93(12):1 786-1 793.
• [4] JEONG W,RHEE K.Hemodynamics of cerebral aneurysms:computat-ionalanalyses of aneurysm progress and treatment[J].Comput Math methods Med,2012,20(12):782-801.
• [5] FROSEN J,TULAMO R,PAETAU A,et al.Saccular intracranial aneurysm:pathology and mechanisms[J].Acta Neuropathologica,2012,12(3):773-786.
• [6] CEBRAL J R,MUT F,WEIR J,et al.Association of hemodynamic character-risticsand cerebral aneurysm rupture[J].AJNR Am J Neuroradiol,2011,17(32):264-270.
• [7] SEIBERT B,TUMMALA R P,CHOW R,et al.Intracranial aneurysms:review of current treatment options and outcomes[J].Front Neurol,2011,8(2):45.
• [8] RAVINDRA V M,DE HAVENON A,GOOLDY T C,et al.Validation of the unruptured intracranial aneurysm treatment score:comparison with real-world cerebrovascular practice[J].J Neurosurg,2018,129(1):100-106.
• [9] CAGNAZZO F,DARGAZANLI C,ROUJEAU T,et al.Pediatric aortic coarctation discovered during endovascular treatment of a ruptured intracranial aneurysm[J].J Neuroradiol,2018,45(1):63-65.
• [10] NUKI Y,TSOU T L,KURIHARA C,et al.Elastase-induced intracranial aneurysms in hypertensive mice[J].Hypertension,2009,54(6):1 337-1 344.
• [11] KOLEGA J,GAO L,MANDELBAUM M,et al.Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial ane-urysm initiation in a rabbit model[J].J Vasc Res,2011,48(5):429-442.
• [12] ZENG Z,KALLMES D F,DURKA M J,et al.Hemodynamics and anatomy of elastase-induced rabbit aneurysm models:similarity to human cerebral aneurysms[J].AJNR Am J Neuroradiol,2011,32(3):595-601.
• [13] TUNGARAZA T E,SINGH R.Unruptured intracra-nial aneurysm and first episode psychosis:The mystery was finally solved[J].Psychiatr Danub,2017,29(Suppl 3):179-182.
• [14] VARBLE N,RAJABZADEH-OGHAZ H,WANG J,et al.Differences in Morphologic and Hemodynamic Characteristics for "PHASES-Based" Intracranial Aneurysm Locations[J].AJNR Am J Neuroradiol,2017,38(11):2 105-2 110.
• [15] CAN A,CASTRO VM,OZDEMIR YH,et al.Association of intracranial aneurysm rupture with smoking duration,intensity,and cessation[J].Neurology,2017,89(13):1 408-1 415.
• [16] STANDHARDT H,BOECHER-SCHWARZ H,GRUBER A,et al.Endovascular treatment of unruptured intracranial aneurysms with Guglielmi detachable coils:short- and long-term results of a single-centreseries[J].Stroke,2008,39(3):899-904.
• [17] ALNAES MS,ISAKSEN J,MARDAL KA,et al.Computation of hemodynamics in the circle of Willis[J].Stroke,2007,38(9):2 500-2 505.
• [18] CHALOUHI N,ALI M S,JABBOUR P M,et al.Biology of intracranial aneurysms:role of inflammation[J].J Cereb Blood Flow Metab,2012,32(9):1 659-1 676.
• [19] CHALOUHI N,ATALLAH E,JABBOUR P,et al.Aspirin for the Prevention of Intracranial Aneurysm Rupture[J].Neurosurgery,2017,64(CN_suppl_1):114-118.
• [20] FENG X,WANG L,GUO E,et al.Passive Smoking Is Not Associated with Risk of Intracranial Aneurysm Rupture in Nonsmoking Women[J].World Neurosurg,2017,107:716-723.
• [21] THEODOTOU C B,SNELLING B M,SUR S,et al.Genetic associations of intracranial aneurysm formation and subarachnoid hemorrhage[J].Asian J Neurosurg,2017,12(3):374-381.
• [22] BOUSSEL L,RAYZ V,MCCULLOCH C,et al.Aneurysm growth occurs at regionof low wall shear stress patient-spjgecific correlation of hemodynamics and growth in a longitudinal study[J].Stroke,2008,39(11):2 997-3 002.
• [23] KANEMATSU Y,KANEMATSU M,KURIHARA C,et al.Critical roles of macrophages in the formation of intracranial aneurysm[J].Stroke,2011,42(1):173-178.
• [24] SCHELLERER V S,LANGHEINRICH M C,ZVER V,et al.Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma[J].Int J Colorectal Dis,2019,34(2):309-317.
• [25] AL-HEETY Q Q,KASABRI V,AKOUR A,et al.Cross-sectional correlates of paraoxonase 1 and soluble intercellular adhesion molecule-1 in metabolic syndrome patients with and without diabetes[J].Ther Adv Endocrinol Metab,2018,9(10):303-310.
• [26] SHIMURA T,SHIBATA M,GONDA K,et al.Prognostic impact of soluble intercellular adhesion molecule-1 in hepatocellular carcinoma[J].Oncol Lett,2018,16(5):6 013-6 018.
• [27] BESSA A S,RAGAB A M,NASSRA R A,et al.Expression levels of aldose reductase enzyme,vascular endothelial growth factor,and intercellular adhesion molecule-1 in the anterior lens capsule of diabetic cataract patients[J].J Cataract Refract Surg,2018,44(12):1 431-1 435.
• [28] CHADORNESHIN H T,GOLESTANI A,JAMAL F,et al.The response of intercellular adhesion molecule-1 to exhaustive submaximal exercise and its correlation with physiological and anthropometric measures[J].J Med Life,2018,11(1):36-41.
• [29] WU H,ZHANG J.miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease[J].Cardiology,2018,139(2):110-118.
• [30] ZHANG H,WANG J,WANG L,et al.Induction of mast cell accumulation by chymase via an enzymatic activity-and intercellular adhesion molecule-1-dependent mechanism[J].Br J Pharmacol,2018,175(4):678-692.
• [31] HUSSEIN A,SAAD K,ASKAR E,et al.Functional variants in intercellular adhesion molecule-1 and toll-like receptor-4 genes are more frequent in children with febrile urinary tract infection with renal parenchymal involvement[J].Acta Paediatr,2018,107(2):339-346.
• [32] ZHAO W,FENG H,GUO S,et al.Danshenol A inhibits TNF-α-induced expression of intercellular adhesion molecule-1(ICAM-1) mediated by NOX4 in endothelial cells[J].Sci Rep,2017,7(1):12 953.
• [33] 阮秋蓉,瞿智玲,朱敏,等.川芎嗪对血管壁细胞血管细胞粘附分子1和单核细胞趋化蛋白1表达的作用及可能机制[J].中国动脉硬化杂志,2010,14(7):560-562.
• [34] LIU J F,TSAO Y T,HOU C H.Fractalkine/CX3CL1 induced intercellular adhesion molecule-1-dependent tumor metastasis through the CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma[J].Oncotarget,2016,8(33):54 136-54 148.
• [35] JOO H K,LEE Y R,CHOI S,et al.Protein kinase C beta Ⅱ upregulates intercellular adhesion molecule-1 via mitochondrial activation in cultured endothelial cells[J].Korean J Physiol Pharmacol,2017,21(4):377-384.
• [36] WU Z,DAI F,REN W,et al.Angiotensin Ⅱ induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1[J].Am J Transl Res,2016,8(1):28-36.
• [37] LEE Y H,BAE S C.Monocyte chemoattractant protein-1 promoter-2518 polymorphism and susceptibility to vasculitis,rheumatoid arthritis,and multiple sclerosis:A meta-analysis[J].Cell Mol Biol (Noisy-le-grand),2016,62(3):65-71.
• [38] KAWABATA K,NISHIMURA I,FUJIWARA T,et al.Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1[J].Eur J Neurosci,2016,43(11):1 499-1 508.
• [39] KAMATH M G,PAI C G,KAMATH A,et al.Monocyte chemoattractant protein-1,transforming growth factor-beta1,nerve growth factor,resistin and hyaluronic acid as serum markers:comparison between recurrent acute and chronic pancreatitis[J].Hepatobiliary Pancreat Dis Int,2016,15(2):209-215.
• [40] ZUNGSONTIPORN N,TELLO R R,ZHANG G,et al.Non-Classical Monocytes and Monocyte Chemoattractant Protein-1 (MCP-1) Correlate with Coronary Artery Calcium Progression in Chronically HIV-1 Infected Adults on Stable Antiretroviral Therapy[J].PLoS One,2016,11(2):e0149143.
• [41] GUPTA R,YADAV A,AGGARWAL A.Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity[J].Clin Rheumatol,2016,35(11):2 707-2 714.
• [42] TSUGAWA K,IMAIZUMI T,WATANABE S,et al.Clarithromycin attenuates the expression of monocyte chemoattractant protein-1 by activating toll-like receptor 4 in human mesangial cells[J].Clin Exp Nephrol,2017,21(4):573-578.
• [43] ZHANG J,WANG C,HA X,et al.DNA methylation of tumor necrosis factor-α,monocyte chemoattractant protein-1,and adiponectin genes in visceral adipose tissue is related to type 2 diabetes in the Xinjiang Uygur population[J].J Diabetes,2017,9(7):699-706.
• [44] MOUCHTOURIS N,LANG M J,BARKLEY K,et al.Predictors of hospital-associated complications prolonging ICU stay in patients with low-grade aneurysmal subarachnoid hemorrhage[J].J Neurosurg,2019,3:1-7.
• [45] LAWTON M T,LANG M J.The future of open vascular neurosurgery:perspectives on cavernous malformations,AVMs,and bypasses for complex aneurysms[J].J Neurosurg,2019,130(5):1 409-1 425.
• [46] KOROSTYNSKI M,PIECHOTA M,MORGA R,et al.Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms[J].J Transl Med,2019,17(1):141.
• [47] WYLER SL,D’IINGILLO SL,LAMB CL,et al.Monocyte chemoattractant protein-1 is not required for liver regeneration after partial hepatectomy[J].J Inflamm (Lond),2016,13(1):28.
• [48] KRIEL J I,FOURIE C M,SCHUTTE A E.Monocyte Chemoattractant Protein-1 and Large Artery Structure and Function in Young Individuals:The African-PREDICT Study[J].J Clin Hypertens (Greenwich),2017,19(1):67-74.
• [49] FISHER C L,DEMEL S L.Nonsteroidal Anti-Inflammatory Drugs:A Potential Pharmacological Treatment for Intracranial Aneurysm[J].Cerebrovasc Dis Extra,2019,9(1):31-45.
• [50] KARASOZEN Y,OSBUN J W,PARADA C A,et al.Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms[J].Am J Hum Genet,2019,104(5):968-976.
• [51] WANG Y,SHI B,LI Y,WANG N.Spontaneous BilateralPneumothorax,Pneumomediastinum,and Subcutaneous Emphysema following Intracranial Aneurysm Clipping under General Anesthesia[J].Anesth Essays Res,2019,13(1):184-187.
• [52] MOROOKA N,UEGURI K,YEE K K L,et al.Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation[J].Biochem Biophys Res Commun,2016,477(4):895-901.
• [53] YOUSUF S D,RASHID F,MATTOO T,et al.Does the Oral Contraceptive Pill Increase Plasma Intercellular Adhesion Molecule-1,Monocyte Chemoattractant Protein-1,and Tumor Necrosis Factor-α Levels in Women with Polycystic Ovary Syndrome:A Pilot Study[J].J Pediatr Adolesc Gynecol,2017,30(1):58-62.
• [54] CHEN H,WANG X,YAO S,et al.The aetiologies of unilateral oculomotor nerve palsy:a clinical analysis on 121 patients[J].Somatosens Mot Res,2019,30:1-7.
• [55] SMITH G,HOH B L,ALBAYRAM M S.Anterior spinal artery aneurysm presenting with spinal subarachnoid hemorrhage in a case ofpolyarteritis nodosa[J].Clin Imaging,2019,56:108-113.
• [56] HAGHIGHAT A,BURKE T H,SPEIRS J WD,et al.Case report:Unusual presentation of haemopericardium with haemodynamic instability secondary to a coronary graft pseudoaneurysm treated by an endovascular approach[J].Eur Heart J Case Rep,2018,2(4):yty147.
• [57] NAGAHARA K,DOBASHI K,ISHIKAWA T,et al.AICAR Attenuates TNFα-Induced Inappropriate Secretion of Monocyte Chemoattractant Protein-1 and Adiponectin in 3T3-L1 Adipocytes[J].J Atheroscler Thromb,2016,23(12):1 345-1 354.
• [58] STUMPF C,RAAZ D,KLINGHAMMER L,et al.Platelet CD40 contributes to enhanced monocyte chemoattractant protein 1 levels in patients with resistant hypertension[J].Eur J Clin Invest,2016,46(6):564-571.
• [59] MIS M,KACA?A A,MILNEROWICZ M,et al.Repeating enlargement,recanalisations,and subarachnoid haemorrhages after middle cerebral artery aneurysm embolisation using pCONus stent and coils-a case report[J].Pol J Radiol,2019,84:e86-e90.
• [60] MENON G,MENON S,HEGDE A.Does Universal Bypass before Carotid Artery Occlusion Obviate the Need for Balloon Test Occlusion:Personal Experience with Extracranial-Intracranial Bypass in 23 Patients[J].J Neurosci Rural Pract,2019,10(2):194-200.
• [61] SABER H,RAJAH G,PALLAM,et al.Utilization and safety of extracranial-intracranial bypass surgery in symptomatic steno-occlusive disorders[J].Brain Circ,2019,5(1):32-35.
• [62] ENRIQUEZ-MARULANDA A,SALEM M M,ASCANIO L C,et al.No differences in effectiveness and safety between pipeline embolization device and stent-assisted coiling for the treatment of communicating segment internal carotid artery aneurysms[J].Neuroradiol J,2019,18:1971400919845368.
• [63] VATTER H,WEIDAUER S,DIAS S,et al.Persistence of the nitric oxide-depe-ndent vasodilator pathway of cerebralvessel safer experimental subara-chnoid hemorrhage[J].Neurosurgery,2007,60(1):179-188.
• [64] NEKRASOV D A,KOROTKIKH A V,BLAGOVISNAIA V A.Hibrid intervention for internal carotid arterystenosis and ipsilateral aneurysm of anterior communicating Artery[J].Angiol Sosud Khir,2019,25(1):75-78.
• [65] TENG J F,WANG K,JIA Z M,et al.Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury[J].Kidney Blood Press Res,2018,43(4):1 084-1 103.
• [66] LIAO C L,CHU Y L,LIN H Y,et al.Bisdemethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-B,MMP-2 and-9 Pathways[J].Anticancer Res,2018,38(7):3 989-3 997.
• [67] YU G Y,WANG X,ZHENG S S,et al.RA190,a Proteasome Subunit ADRM1 Inhibitor,Suppresses Intrahepatic Cholangiocarcinoma by Inducing NF-KB-Mediated Cell Apoptosis[J].Cell Physiol Biochem,2018,47(3):1 152-1 166.
• [68] CHENG L,ZHOU S,ZHAO Y,et al.Tanshinone IIA attenuates osteoclastogenesis in ovariectomized mice by inactivating NF-kB and Akt signaling pathways[J].Am J Transl Res,2018,10(5):1 457-1 468.
• [69] LIU W,WU Y H,ZHANG L,et al.MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling[J].Oncotarget,2018,9(35):23 944-23 959.