中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2001年
3期
169-172
,共4页
戴军%高润霖%宋来凤%阮英茆%陈纪林%李永力%孟亮%唐承君%史瑞文%汤键
戴軍%高潤霖%宋來鳳%阮英茆%陳紀林%李永力%孟亮%唐承君%史瑞文%湯鍵
대군%고윤림%송래봉%원영묘%진기림%리영력%맹량%당승군%사서문%탕건
再狭窄%支架%基因治疗%一氧化氮合酶
再狹窄%支架%基因治療%一氧化氮閤酶
재협착%지가%기인치료%일양화담합매
目的 为评价蛋白涂层金属支架携带质粒介导的诱导性一氧化氮合酶（iNOS）基因局部转染血管壁,预防冠状动脉内血管成形术后再狭窄的效果。方法 金属支架涂层为胶联明胶制成。载体为去内毒素纯化pcDNA3。采用标准球囊导管技术，将吸附有质粒介导的人肝脏的iNOS基因(pcDNA3hepiNOS)涂层支架置入小型猪(n=9)冠状动脉前降支中段,以相同方法置入单纯蛋白涂层支架做为对照组(n=9)，支架与血管直径之比为1.1～1.3:1。结果 在支架置入后7d，RT-PCR检测和免疫组织化学染色，证实在pcDNA3hepiNOS转染的血管段有iNOSmRNA的表达和iNOS蛋白生成,而远离器官则无基因的表达。3个月时冠状动脉造影显示：转染pcDNA3hepiNOS组(n=5)无再狭窄发生，而对照组均发生显著的再狭窄。组织病理学形态分析结果显示：pcDNA3hepiNOS组新生内膜面积(1.7±0.8)mm2、平均百分狭窄面积(26.5±7.5)%、平均管腔狭窄百分数(41.2±16.5)%，均较对照组小，对照组分别为（2.8±0.8）mm2，P<0.05；（94.2±14.3）％，P<0.001；（88.0±16.6）%，P<0.001；比较内膜面积/中膜面积比值（I/M）治疗组较对照组减少了59.8%。结论 在小型猪模型使用蛋白涂层支架携带纯化质粒介导的iNOS基因可直接导入血管成形部位，并能预防内膜过度增殖，从而预防再狭窄的发生。
目的 為評價蛋白塗層金屬支架攜帶質粒介導的誘導性一氧化氮閤酶（iNOS）基因跼部轉染血管壁,預防冠狀動脈內血管成形術後再狹窄的效果。方法 金屬支架塗層為膠聯明膠製成。載體為去內毒素純化pcDNA3。採用標準毬囊導管技術，將吸附有質粒介導的人肝髒的iNOS基因(pcDNA3hepiNOS)塗層支架置入小型豬(n=9)冠狀動脈前降支中段,以相同方法置入單純蛋白塗層支架做為對照組(n=9)，支架與血管直徑之比為1.1～1.3:1。結果 在支架置入後7d，RT-PCR檢測和免疫組織化學染色，證實在pcDNA3hepiNOS轉染的血管段有iNOSmRNA的錶達和iNOS蛋白生成,而遠離器官則無基因的錶達。3箇月時冠狀動脈造影顯示：轉染pcDNA3hepiNOS組(n=5)無再狹窄髮生，而對照組均髮生顯著的再狹窄。組織病理學形態分析結果顯示：pcDNA3hepiNOS組新生內膜麵積(1.7±0.8)mm2、平均百分狹窄麵積(26.5±7.5)%、平均管腔狹窄百分數(41.2±16.5)%，均較對照組小，對照組分彆為（2.8±0.8）mm2，P<0.05；（94.2±14.3）％，P<0.001；（88.0±16.6）%，P<0.001；比較內膜麵積/中膜麵積比值（I/M）治療組較對照組減少瞭59.8%。結論 在小型豬模型使用蛋白塗層支架攜帶純化質粒介導的iNOS基因可直接導入血管成形部位，併能預防內膜過度增殖，從而預防再狹窄的髮生。
목적 위평개단백도층금속지가휴대질립개도적유도성일양화담합매（iNOS）기인국부전염혈관벽,예방관상동맥내혈관성형술후재협착적효과。방법 금속지가도층위효련명효제성。재체위거내독소순화pcDNA3。채용표준구낭도관기술，장흡부유질립개도적인간장적iNOS기인(pcDNA3hepiNOS)도층지가치입소형저(n=9)관상동맥전강지중단,이상동방법치입단순단백도층지가주위대조조(n=9)，지가여혈관직경지비위1.1～1.3:1。결과 재지가치입후7d，RT-PCR검측화면역조직화학염색，증실재pcDNA3hepiNOS전염적혈관단유iNOSmRNA적표체화iNOS단백생성,이원리기관칙무기인적표체。3개월시관상동맥조영현시：전염pcDNA3hepiNOS조(n=5)무재협착발생，이대조조균발생현저적재협착。조직병이학형태분석결과현시：pcDNA3hepiNOS조신생내막면적(1.7±0.8)mm2、평균백분협착면적(26.5±7.5)%、평균관강협착백분수(41.2±16.5)%，균교대조조소，대조조분별위（2.8±0.8）mm2，P<0.05；（94.2±14.3）％，P<0.001；（88.0±16.6）%，P<0.001；비교내막면적/중막면적비치（I/M）치료조교대조조감소료59.8%。결론 재소형저모형사용단백도층지가휴대순화질립개도적iNOS기인가직접도입혈관성형부위，병능예방내막과도증식，종이예방재협착적발생。
Objective To assess the effect of local transfer ofplasmid-mediated inducible Nitric Oxide synthase gene using protein-coated metallic stents of inhibiting neointimal hyperplasia after coronary angioplasty. Methods The metallic stent was coated by cross-linked gelatin and mounted on 3.0 mm PTCA balloon,then endotoxin-free ultrapure plasmid pcDNA3hepiNOS was absorbed on the stent. Protein-coated stainless steel stents were used as controls. All stents were implanted into the middle segment of LAD. The ratio of balloon to vessel diameter was 1.1－1.3:1. Results At the 7th day after stenting, RT-PCR and immunohistochemical staining confirmed the expression of iNOS mRNA and presence of its protein at gene transferred vessels (n=2), but there was no expression in remote organs. After 3 months of stenting coronary angiograms showed that there was no restenosis in all animals transferred plasmid pcDNA3hepiNOS(n=5) while restenosis developed in all animals of the control group (n=5). Morphometric analysis showed that lumen diameter loss (0.61±0.30) mm vs (1.58±0.31) mm (P<0.001), residual lumen diameter (1.00±0.51) mm vs (0.36±0.32) mm (P<0.05), neointimal area (1.65±0.83) mm2 vs (2.83±0.83) mm2 (P<0.05), mean percentage of area stenosis (26.45±7.45) mm2 vs (94.2±14.3) mm2 (P<0.001) were significantly less than those in control group. The proportion of the neointimal area to media area(I/M) reduced to 59.84% in pcDNA3hepiNOS group. Conclusions Local plasmid-mediated human iNOS gene transferred with protein-coated metallic stents significantly inhibited intimal hyperplasia,which was usually a causative factor of retenosis after coronary angioplasty, in mini-swine model.
