局部应用血管紧张素Ⅱ_1型受体反义寡核苷酸对大鼠颈动脉损伤后内膜增生的影响

THE INHIBITORY EFFECT OF ANTISENSE ANGIOTENSIN Ⅱ TYPE I RECEPTOR PHOSPHORTHIOATE OLIGODEOXYNUCLEOTIDE ON INTIMAL HYPERPLASIA IN RAT CAROTID ARTERY AFTER NITROGEN DEYING INJURY

目的 观察血管紧张素Ⅱ1型受体的反义寡脱氧核苷酸对氮气干燥后的大鼠颈动脉内膜增生的影响 ,以期为临床防治再狭窄提供一种新的基因治疗策略。方法 动物分为六组 :反义组、正义组、错配组、阳离子脂质体DOTAP组、对照组和假手术组 ,以压力为驱动系统 ,阳离子脂质体DOTAP为转染系统 ,局部、靶向将不同反义寡脱氧核苷酸转染于大鼠颈动脉内膜损伤段 ,阳离子脂质体DOTAP组仅应用DOTAP ,对照组剥脱内膜后不作任何处理 ,假手术组仅用 0 .9%生理盐水冲洗颈动脉。饲养 2周 ,处死动物 ,对所取的血管段进行组织切片和HE染色 ,在显微镜下进行观察和计算机彩色图像处理系统进行图像分析 ,计算血管腔面积、内膜面积、内膜 /中膜面积比值、最大内膜厚度、内膜 /中膜厚度比值和内膜覆盖率等指标并进行统计分析。结果 反义组管腔面积大于正义组、错配组、阳离子脂质体DOTAP组及对照组 ,小于假手术组 (P <0 .0 5) ;内膜面积、内膜 /中膜面积比值、最大内膜厚度、内膜 /中膜厚度比值和内膜覆盖率 :反义组小于正义组、错配组、阳离子脂质体DOTAP组及对照组 (P <0 .0 5) ;而正义组、错配组、阳离子脂质体DOTAP组与对照组两两相比上述指标无明显差异 (P >0 .0 5) ;

Objective To evaluate the effect of antisense angiotensin Ⅱ type Ⅰ (AT 1R) oligodeoxynucleotide (ODN) on intimal hyperplasia in rat carotid artery after nitrogen drying injury.Methods Sixty rats were randomized into six groups:antisense(A) group,sense(S) group,mismatch(M)group,cationic lipid DOTAP(D) group,control(C) group and false(F) group.Different ODN was applied locally through double balloon pressure drive system and DOTAP delivery system,group C received only nitrogen drying endothelial.group D delivery DOTAP alone,group F used 0.9 percent NaCl irrigation left common carotid.The rats were fed with routine diet.After two weeks,the animals were killed and defined segmient of artery was sectioned and the histological sections were stained with HE staining.The cross-section of artery was examined microscopically and the image was digitalized by color image analysis system.The lumen area,the ratios of intima/media area,intima thickness,the ratios of intima/media thickness and the covery ratios of intima were calculated and analyzed statistically among the groups.Result The lumen area of group A was larger than that of group S,group M,group D and group C(P<0.05);The intima area,the ratios of intima/media area,intima thickness,the ratios of intima/media thickness and the covery ratios of intima of group A were less than that of group S,group M, group D and group C(P<0.01).Conclusion The AT 1R plays an important role in the mechanism of intima hyperplasia.Antisense ODN of AT 1R significantly inhibited the intimal hyperplasia in injury rat carotid artery in sequence-specific manner.The investigation provides a new genetic therapeutic strategy for the prevention of restenosis after angioplasty.