【摘要】目的观察α-氰基丙烯酸酯(α-cyanoacrylate,α-CA)血管外支架对兔动静脉内瘘(arteriovenous fistula,AVF)近吻合口静脉内膜增生的影响。方法取20 只成年雄性家兔，随机分为2 组，每组10 只。①对照组：颈总动脉、颈总静脉端端吻合建立AVF。②α-CA 组：AVF 建立后，近吻合口静脉外周表面应用α-CA 涂层建立血管外支架。分别于手术中、手术后1 月，彩色多普勒超声检测近吻合口静脉的内径及收缩期峰值血流速度，并于手术后1 个月取AVF 近吻合口静脉作如下检测：HE 染色测量其内膜厚度、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)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达。结果AVF 手术后1 个月，彩色多普勒超声检测显示对照组AVF 近吻合口静脉内径[(3.50±0.30)mm]较α-CA 组[(3.22±0.23) mm]明显增加(t=2.326,P=0.032)；对照组AVF 近吻合口静脉收缩期峰值血流速度[(512.0±83.6)mm/s]较α-CA 组[(668.6±64.1) mm/s]明显降低(t=4,701,P＜0.001)。HE 染色显示对照组AVF 近吻合口静脉内膜厚度[(35.3±6.1)]μm 较α-CA 组[(24.8±5.6)μm]明显增加(t=3.987,P=0.001)；免疫组化法显示对照组AVF 近吻合口静脉内膜PCNA、α-SMA 的阳性率[(20.5±3.9)%、(25.9±4.7)%]明显高于α-CA组[(14.2±3.1)%、(16.5±3.7)%]，组间比较，差异均有统计学意义(t值分别为3.993、4.948，P值分别为0.001、<0.001)。结论α-氰基丙烯酸酯血管外支架能够减轻家兔颈总动静脉内瘘近吻合口静脉内膜增生。
【Abstract】Objective To observe the effect of extravascular stent coated with α-cyanoacrylate (α-CA) on venous intimal hyperplasia in juxta-anastomotic veins of arteriovenous fistula (AVF) in rabbits. Method Twenty adult male rabbits were randomly divided into control group (n=10) and α-CA group (n=10). AVF was created by end- to- end anastomosis of common carotid artery and common jugular vein in animals of both groups. In the α-CA group, extravascular stent coated with α-CA was applied to the outer surface of juxtaanastomotic vein. Color Doppler ultrasonography was used to examine the diameter and peak systolic flow velocity of the juxta-anastomotic vein immediately after the operation and after the operation for one month. The juxta- anastomotic vein was taken after the operation for one month, the intimal thickness and the ratio of intima/ media thickness were measured after hematoxylin-eosin (HE) staining, and the expression of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected by immunohistochemistry. Result After the operation for one month, color Doppler ultrasonography showed that the diameter of juxtaanastomotic vein of AVF was 3.50±0.30 mm in the control group higher than the diameter of 3.22±0.23 mm in the α-CA group (t=2.326, P=0.032); the peak systolic flow velocity in juxta- anastomotic vein of AVF was 512.0±83.6mm/s in the control group, lower than the velocity of 668.6±64.1mm/s in the α-CA group (t=4,701,P＜0.001). H-E staining of the intimal in the juxta-anastomotic vein showed that the intimal thickness was 35.3±6.1μm in the control group, higher than that of 24.8±5.6μm in the α-CA group(t=3.987, P=0.001). Immu-nohistochemistry of the intimal in the juxta- anastomotic vein showed that the positive expression rates of PCNA and α-SMA in the in intimal cells were 20.5±3.9% and 25.9± 4.7% respectively in the control group, higher than those of 14.2±3.1% and 16.5±3.7% respectively in the α-CA group (t=3.993 and 4.948 respectively, P=0.001 and <0.001 respectively). Conclusion Extravascular stent coated with α-cyanoacrylate can prevent
juxta-anastomotic vein of the AVF from intimal hyperplasia in rabbits.
[1] Badero OJ, Salifu MO, Wasse H, et al. Frequency of swing-segment stenosis in referred dialysis patients with angiographically documented lesions[J]. Am J Kidney Dis, 2008, 51 (1): 93-98.
[2] 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.
[3] Mima A. Hemodialysis vascular access dysfunction: molecular mechanisms and treatment [J]. Cardiovasc Eng Technol, 2017, 8 (3): 280-294.
[4] Karayannacos PE, Hostetler JR, Bond MG, et al. Late failure in vein grafts: mediating factors in subendothelial fibromuscular hyperplasia[J]. Ann Surg, 1978, 187 (2): 183-188.
[5] Kahraman N, Yumun G, Gucu A, et al. Administration of perivascular cyanoacrylate for the prevention of cellular damage in saphenous vein grafts: an experimental model[J]. Cardiovasc J Afr, 2016, 27 (3): 159-163. DOI:10.5830/CVJA-2015-078.
[6] Dai L, Gao M, Gu C, et al. Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting[J]. Eur J Cardiothorac Surg, 2016, 49 (2): 675-681.
[7] Liu SQ, Ruan YY, Tang D, et al. A possible role of initial cell death due to mechanical stretch in the regulation of subsequent cell proliferation in experimental vein grafts[J]. Biomech Model Mechanobiol, 2002, 1 (1): 17-27.
[8] Shyu KG. Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes[J]. Clin Sci (Lond), 2009, 116 (5): 377-389.
[9] 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.
[10] 郑家豪,潘文标,吕一峰,等.血管外支架预防猪大隐静脉移植血管再狭窄的实验研究[J].中国胸心血管外科临床杂志,2006,13(6):405-408.
[11] Boire TC, Balikov DA, Lee Y, et al. Biomaterial-Based Approaches to Address Vein Graft and Hemodialysis Access Failures[J]. Macromol Rapid Commun, 2016, 37 (23): 1860-1880.
[12] Sato A, Kawamoto S, Watanabe M, et al. A novel biodegradable external mesh stent improved long-term patency of vein grafts by inhibiting intimal-medial hyperplasia in an experimental canine model[J]. Gen Thorac Cardiovasc Surg, 2016, 64 (1): 1-9.
[13] 戴龙圣,高铭鑫,于文渊,等.医用化学胶外支架改善冠状动脉旁路移植术后静脉旁路移植血管通畅率的随访研究[J].中华胸心血管外科杂志,2019,36(6):405-408.
[14] Frismantiene A, Philippova M, Erne P, et al. Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity[J]. Cell Signal, 2018, 52: 48-64.
