目的 探讨应用No-touch技术(no-touch technique,NTT)分离静脉构建家兔颈总动静脉内瘘(arteriovenous fistula,AVF)对手术后早期近吻合口静脉炎症反应及内膜增生的影响。方法 24只雄性家兔随机分为常规技术(conventional technique,CT)组和NTT组分别构建家兔颈总AVF,每组12只。手术后第7天每组各随机取6只家兔AVF近吻合口静脉,定量逆转录聚合酶链式反应检测其Toll样受体4(toll-like receptor 4,TLR4)、核因子-κB p65(nuclear factor-κB p65,NF-κB p65)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)mRNA表达;手术后第21天每组各取剩余6只家兔AVF近吻合口静脉,苏木精-伊红染色测量其血管内膜厚度、内中膜厚度比值,免疫组化法检测其内膜增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达。 结果 CT组AVF近吻合口静脉内膜厚度、内中膜厚度比值较NTT组均明显增加(t=2.726、3.145,P=0.021、0.010);CT组AVF近吻合口静脉内膜细胞PCNA的阳性表达率明显高于NTT组(t=4.242,P=0.002),CT组AVF近吻合口静脉TLR4、NF-κB p65、TNF-α、IL-1β mRNA的相对表达量均明显高于NTT组(t=13.457、12.116、9.693、9.678,均P<0.001)。 结论 比较常规技术,应用No-touch技术分离静脉构建家兔颈总AVF能够减轻手术后早期近吻合口静脉炎症反应及内膜增生。
Objective To investigate the effects on the early postoperative juxta-anastomotic venous inflammatory response and intimal hyperplasia of arteriovenous fistula (AVF) in rabbits constructed with the no⁃touch technique (NTT) to dissect veins. Methods Twenty-four male rabbits were randomly divided into conventional technique (CT) group and NTT group, with 12 rabbits in each group. AVFs were constructed with CT to dissect the veins in CT group, and with NTT to dissect veins in NTT group. At the 7th day after the operation, the juxta-anastomotic veins of AVFs were randomly collected in 6 rabbits from each group. The mRNA expressions of toll-like receptor 4 (TLR4), nuclear factor⁃κB p65 (NF⁃κB p65), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the juxta-anastomotic veins were measured by quantitative reverse transcription PCR. At the 21st day after the operation, juxta-anastomotic veins of AVFs were collected in the remaining 6 rabbits from each group, the intimal thickness and the ratio of intima-media thickness were measured after hematoxylin-eosin staining, and the expression of proliferating cell nuclear antigen (PCNA) in the intima was detected by immunohistochemistry. Results The intimal thickness and intima-media thickness ratio of juxta-anastomotic veins were 23.7±3.1μm and 26.5±2.3% respectively in the CT group, significantly higher than those of(19.5±2.2)μm and 22.7±1.9% in the NTT group (t=2.726 and 3.145 respectively; P=0.021 and 0.010 respectively). The positive expression rate of PCNA in the intimal cells of juxta-anastomotic veins was 20.2±2.3% in the CT group, significantly higher than that of 15.2±1.8% in the NTT group (t=4.242, P=0.002). The relative mRNA expressions of TLR4, NF⁃κB p65, TNF-α and IL-1β of juxta-anastomotic veins in the CT group were also significantly higher than those in the NTT group (t=13.457, 12.116, 9.693 and 9.678 respectively; P<0.001). Conclusions Compared with CT, dissection of veins using NTT for the construction AVF in rabbits could attenuate the early postoperative juxta-anastomotic venous inflammatory response and intimal hyperplasia.
[1] Quencer KB, Arici M. Arteriovenous Fistulas and Their Characteristic Sites of Stenosis[J]. AJR Am J Roentgenol, 2015, 205 (4): 726-734.
[2] Gameiro J, Ibeas J. Factors affecting arteriovenous fistula dysfunction: A narrative review[J]. J Vasc Access, 2020, 21 (2): 134-147.
[3] Cunnane CV, Cunnane EM, Walsh MT. A Review of the hemodynamic factors believed to contribute to vascular access dysfunction[J]. Cardiovasc Eng Technol, 2017, 8 (3): 280-294.
[4] Satish M, Gunasekar P, Agrawal DK. Pro-inflammatory and pro-resolving mechanisms in the immunopathology of arteriovenous fistula maturation[J]. Expert Rev Cardiovasc Ther, 2019, 17 (5): 369-376.
[5] Nguyen M, Thankam FG, Agrawal DK. Sterile inflammation in the pathogenesis of maturation failure of arteriovenous fistula[J]. J Mol Med (Berl), 2021, 99 (6): 729-741.
[6] Souza D. A new no-touch preparation technique. Technical notes[J]. Scand J Thorac Cardiovasc Surg, 1996, 30 (1): 41-44.
[7] Souza DS, Christofferson RH, Bomfim V, et al. "No-touch" technique using saphenous vein harvested with its surrounding tissue for coronary artery bypass grafting maintains an intact endothelium[J]. Scand Cardiovasc J, 1999, 33 (6): 323-329.
[8] ugaya A, Ohno N, Yashiro T, et al. Morphological Changes in Endothelial Cell Organelles in a No-Touch Saphenous Vein Graft[J]. Braz J Cardiovasc Surg, 2022, 37 (Spec 1): 49-56.
[9] Verma S, Lovren F, Pan Y, et al. Pedicled no-touch saphenous vein graft harvest limits vascular smooth muscle cell activation: the PATENT saphenous vein graft study[J]. Eur J Cardiothorac Surg, 2014, 45 (4): 717-725.
[10] de Vries MR, Simons KH, Jukema JW, et al. Vein graft failure: from pathophysiology to clinical outcomes[J]. Nat Rev Cardiol, 2016, 13 (8): 451-470.
[11] Zhao TY, Bu JQ, Gu JJ, et al. The Short-Term Patency Rate of a Saphenous Vein Bridge Using the No-Touch Technique in off-Pump Coronary Artery Bypass Grafting in Vein Harvesting[J]. Int J Gen Med, 2021, 14: 2281-2288.
[12] Samano N, Geijer H, Liden M, et al. The no-touch saphenous vein for coronary artery bypass grafting maintains a patency, after 16 years, comparable to the left internal thoracic artery: A randomized trial[J]. J Thorac Cardiovasc Surg, 2015, 150 (4): 880-888.
[13] McGah PM, Leotta DF, Beach KW, et al. Incomplete restoration of homeostatic shear stress within arteriovenous fistulae[J]. J Biomech Eng, 2013, 135 (1): 011005.
[14] Dashwood MR, Tsui JC. 'No-touch' saphenous vein harvesting improves graft performance in patients undergoing coronary artery bypass surgery: a journey from bedside to bench[J]. Vascul Pharmacol, 2013, 58 (3): 240-250.
[15] Eltzschig HK, Carmeliet P. Hypoxia and inflammation[J]. N Engl J Med, 2011, 364 (7): 656-665.
[16] Jiang Q, Yang Y, Sun H, et al. Stable Hemodynamics within "No-Touch" Saphenous Vein Graft[J]. Ann Thorac Cardiovasc Surg, 2020, 26 (2): 88-94.
[17] Ward AO, Caputo M, Angelini GD, et al. Activation and inflammation of the venous endothelium in vein graft disease[J]. Atherosclerosis, 2017, 265: 266-274.
[18] McQueen LW, Ladak SS, Zakkar M. Acute shear stress and vein graft disease[J]. Int J Biochem Cell Biol, 2022, 144: 106173.
[19] Wang ZV, Scherer PE. Adiponectin, the past two decades[J]. J Mol Cell Biol, 2016, 8 (2): 93-100.
[20] Mikami T, Furuhashi M, Sakai A, et al. Antiatherosclerotic Phenotype of Perivascular Adipose Tissue Surrounding the Saphenous Vein in Coronary Artery Bypass Grafting[J]. J Am Heart Assoc, 2021, 10 (7): e018905.
[21] Hori M, Nishida K. Toll-like receptor signaling: defensive or offensive for the heart?[J]. Circ Res, 2008, 102 (2): 137-139.
[22] Kumar A, Takada Y, Boriek AM, et al. Nuclear factor-kappaB: its role in health and disease[J]. J Mol Med (Berl), 2004, 82 (7): 434-448.
[23] Panicker N, Sarkar S, Harischandra DS, et al. Fyn kinase regulates misfolded alpha-synuclein uptake and NLRP3 inflammasome activation in microglia[J]. J Exp Med, 2019, 216 (6): 1411-1430.
[24] Hernanz R, Martinez-Revelles S, Palacios R, et al. Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension[J]. Br J Pharmacol, 2015, 172 (12): 3159-3176.
[25] Park SY, Jeong MS, Han CW, et al. Structural and Functional Insight into Proliferating Cell Nuclear Antigen[J]. J Microbiol Biotechnol, 2016, 26 (4): 637-647.