Apoptosis and proliferation expression in autogenous vein grafts of low shear stress in a canine model

目的：目的观察低切应力（t）对犬自体静脉移植物动脉移植后内膜/中层细胞凋亡和增殖的影响。材料和方法：8只比格犬，将自体股静脉逆行植入股动脉。4条静脉移植物在正常径流条件下植入（对照组），另外4条静脉移植物在低t的不良径流条件下植入（不良径流组）。移植物在4周后进行光镜和免疫组织化学分析（Ki-67和末端转移酶介导的dUTP缺口末端标记[TUNEL]方法）。结果如下：对照组植入时的平均血流量和t分别为26.25^^+__-3.7 mL/min和74.87 ^^+_-10.7 dyne/cm^2，而流出不良组的平均血流量和t显著降低至11.25 ^^+__-2.8 mL/min和32.08^^+_-8.1 dyne/cm^2，P < 0.05。在移植物植入后4周，流出不足组的内膜/中膜厚度明显比对照组增生（489.96^^+_-5.9 vs 331.7^^+_-8.3 mm; p < 0.0001）。Ki-67的表达显示，低t组移植物的细胞周期水平显著高于正常t组（3.0^^+__-0.4 vs 1.5^^+_-0.3%; p < 0.05）。低t组移植物的细胞凋亡率也明显较高（0.53^^+__-0.1vs0.21 ^^+__-0.04%; p < 0.05）。结论：暴露于低t的静脉移植物刺激SMC增殖和凋亡的高速率，诱导内膜/中膜厚度的持续进展。

Objective : To evaluate the effect of low wall shear stress (t) in the expression of apoptosis and the proliferation ratio of intimal/medial layer of the arterially transplanted autogenous vein grafts in dogs. Material and Methods : A reversed autogenous femoral vein was implanted in the femoral artery of 8 beagle dogs. Four vein grafts were implanted under normal runoff conditions (control group), and another four vein grafts were implanted under conditions of poor runoff with low t(poor runoff group). Grafts were explanted four weeks later and analyzed by light microscopy and immunohistochemistry (Ki-67 and terminal transferase-mediated dUTP nick end labeling [TUNEL] methods). Results : Mean blood flow and t at implantation in the control group were 26.25^^+__-3.7 mL/min and 74.87 ^^+__-10.7 dyne/cm^2, respectively, whereas mean blood flow and t in the poor runoff group decreased significantly to 11.25 ^^+__-2.8 mL/min and 32.08^^+__-8.1 dyne/cm^2, respectively(p < 0.05). The intimal/medial thickness at four weeks after graft implantation in the poor runoff group was significantly more hyperplastic than the control group(489.96^^+__-5.9 vs 331.7^^+__-8.3mm ; p < 0.0001). Expression of Ki-67 showed a significantly higher level of cell cycling in grafts exposed to low t than in the normal t (3.0^^+__-0.4 vs 1.5^^+__-0.3 % ; p < 0.05). Apoptosis ratios were also significantly higher in the grafts exposed to low t (0.53^^+__-0.1 vs 0.21^^+__-0.04 %; p < 0.05). Conclusion : Vein grafts exposed to low t stimulated high rates of SMC proliferation and apoptosis, inducing persistent progression of intimal/medial thickness.