Pro-UK基因抑制静脉移植物细胞增生的实验研究

The experimental study of Pro-UK gene in inhibiting hyperplasia of vein bypass graft

目的：探讨ＰｒｏＵＫ 基因对静脉桥移植物细胞增生的影响。方法：３００ ～３５０ｇ Ｗｉｓｔａｒ 大鼠４２ 只，取下大鼠颈静脉，两端阻断后，用含Ａｄｖ５ＣＭＶ 质粒（ 对照组，２１ 只） 或含Ａｄｖ５ＣＭＶＰｒｏＵＫ 质粒（ 治疗组，２１ 只） 的溶液扩张静脉，使溶液在静脉腔内滞留３０ 分钟，然后置于同一大鼠的颈总动脉。术后２８ 天，取静脉移植物行尿激酶原活性测定，观察ＰｒｏＵＫ 基因的表达。行３ＨＴＤＲ 掺入量测定和病理分析，观察静脉桥管壁增厚情况。结果：术后２８ 天，治疗组可测到较高水平的ＰｒｏＵＫ 表达（２６５ｉｕｇｔｉｓｓｕｅ） ，对照组未测到ＰｒｏＵＫ 活性。虽然两组的管壁均有不同程度的增厚，但治疗组管壁增厚明显小于对照组（ Ｐ＜ ０ ．０１） ，而管腔面积明显大于对照组（ Ｐ＜ ０ ．０１） 。３ＨＴＤＲ 掺入量比对照组低。治疗组１０ 条静脉桥全部畅通，而对照组１０ 条静脉桥有２ 条发生闭塞。结论：用静脉桥局部直接转基因的方法将腺病毒载体介导的ＰｒｏＵＫ基因转入静脉桥可明显抑制细胞增生，是提高静脉桥通畅率的一个有效方法。

Aim:To evaluate the role of Pro-UK gene in inhibiting hyperplasia of vein bypass graft.Materials:42 wister rats underwent implantation of reversed autologous jugular vein interposition grafts in the common carotid artery.Jugular veins were exercised and distended with solution containing either Adv 5-CMV(control group) or Adv 5-CMV/Pro-UK(treatment group) for 30 minutes,then the jugular veins were reversed and interposed into the divided carotid arteries.Proximal and distal anastomoses were performed in an end-to-end fashion with interrupted 11-0 polypropylene sutures.On 28th day after surgery,the vein grafts of two groups were explanted to examine the presence of Pro-UK gene expression and evaluate the 3 H-TDR incorporation and perform histologic analysis.Results:The amount of Pro UK gene expression in treatment group was 265iu/g tissue,Pro UK activity was not detected in the vein graft in control group.The amount of 3 H TDR incorporation in control group was higher than that of treatment group.Histologic analysis demonstrated that the vein graft of two groups exhibited vein wall thickening,but the degree of hyperplasia was predominant in control group than that in treatment group.The occlusion rate of grafts in control group was 20%.All grafts in treatment group were patent.Conclusion:Mediated by adenovirus vector after direct gene transfer into vein graft,Pro-UK gene expression could inhibit hyperplasia of vein bypass graft.Therefore,this method could effectively improve venous graft patency.