植入携带有治疗性腺病毒的包裹支架对猪冠状动脉再狭窄的预防作用

Stent-based local delivery of therapeutic adenovirus effectively reduces neointimal proliferation in porcine coronaries

目的寻找一种有效转送治疗基因到所扩张冠状动扩脉的靶部位的方法,以预防冠状动脉损伤后再狭窄。方法大白猪14只,随机分治疗组(包裹支架)和对照组(非包裹支架),每组7只,治疗组用高分子聚合物phosphorylocholine包裹不锈钢丝的包裹支架,对照组用非包裹支架,经复制缺陷的重组腺病毒RadTIMP-3处理后,植入猪的冠状动脉,4周后,行冠状动脉造影,取新鲜的心脏用福尔马林固定,进行组织形态分析。结果治疗组的血管腔内径平均值为(2.32±0.185) mm, 而非包裹支架的对照组平均直径为(1.79±0.31) mm,治疗组显著高于对照组,P=0.014。TiMP-3治疗组冠状动脉内膜的厚度为(0.34±0.17) mm,对照组为(0.81±0.32) mm,显著高于治疗组,P= 0.0059。结论经PC包裹支架输送含有TIMP-3基因的腺病毒到冠状动脉,可有效地抑制内膜平滑肌细胞的增生,减轻再狭窄。

Objective To find an effective means for delivering therapeutic genes of Tissue inhibitor of metalloproteinase-3 (TIMP-3) to the target sites of the dilated coronary artery forthepurposeofpreventingrestenosisoftheinjuredartery.Methods A stainless steel stent coated with a high-molecular-mass polymer phosphorylocholine, after treatment with recombi-nant replication-defective adenovirus designated as RAD TIMP-3, was implanted into the coronary arteries of 7 pigs (therapygroup). Another 7 pigs serving as the control group received impantation of uncoated stent. In both groups, coronary arteryangiography was performed before withdrawal of intubation and 28 days after the implantation. For the purpose of planimetricanalysis, the stented coronary arteries were isolated and fixed followed by resin embedding. Six sections were obtained foreach stent for morphological assessment. Results The lumen diameter of the therapy group was 2.32±0.18 mm, significantlygreater than that of the control group (1.79±0.31 mm, P=0.014). The neointimal thickness was smaller in the therapy group (0.34±0.17 mm vs 0.81±0.32 mm, P=0.0 059). Conclusions The stent with biosynthetic coating effectively promotes TIMP3AdVtransductionandtranscription,whicheffectivelyreducesneointimalproliferation,thusconfirmingitsroleintheprevention of in-stent restenosis. This maneuver may offer an alternative to conventional drug coatings for preventing restenosis.