摘要
目的探讨靶向超声介导VEGF165cDNA基因治疗大鼠心肌缺血的可行性。方法将60只心肌缺血的雄性SD大鼠分为3组:超声介导基因组(采用超声破坏微泡造影剂的方法将VEGF165cDNA基因转染大鼠)、单纯基因组(尾静脉输入同等量携带VEGF165cDNA基因的造影剂)、对照组。每组又分为24h后处死组和14d后处死组,每小组为10只。处死后分别行坏死区中性粒细胞记数,梗死区质量比测定,免疫组织化学检测缺血心肌中的VEGF蛋白表达,缺血心肌区域毛细血管记数。结果24h处死组:超声介导基因组坏死区中性粒细胞平均为(59.30±7.70)个/高倍视野,单纯基因组为(62.53±7.50)个/高倍视野。14d后处死组:超声介导基因组梗死区质量比明显小于单纯基因组,单纯基因组又明显小于对照组。超声介导基因组有大量VEGF蛋白阳性反应的棕褐色颗粒,而单纯基因组VEGF蛋白阳性反应的棕褐色颗粒少于超声介导基因组。结论超声介导微泡造影剂携带VEGF165cDNA基因能提高基因转染率,促进缺血区毛细血管再生,减少心肌梗死面积,对缺血区炎性细胞的浸润也有一些影响,且基因的转染>24h。
Objective To study the feasibility of targeted ultrasound delivering VEGF105 cDNA gene to myocardial ischemia-reperfusion injury of rats. Methods Sixty male SD rat models of myocardial ischemia- reperfusion injury （I/R） were divided into three groups. 5% sonicated human albumin microbubble of attached with VEGF105 cDNA was infused into the tail vein of rats with or without simultaneous ultrasound destruction microbubbles. The third group served as control group. Every group was divided further into two groups. One group（24 h group） killed after 24 hours and another group（14 d group） were killed after 14 day and examined for VEGF protein expression by immunohistochemical technique. Microvascular density （MVD ） and polymorphonuclears（PMN） were counted in the infarcted area. The area of myocardial necrosis was measured. Results In 24 h group the infiltration of PMN was （59.30 ± 7.70）/HP in received ultrasound-mediated microbubbles group but without received ultrasound-mediated microbubbles was （62.53± 7.50）/HP. In 14 d group VEGF protein exprcssion and MVD were higher in group which received uhrasound mediated microbubble destruction for delivering VEGF105 cDNA than without ultrasound-mediated group and in controls. Conclusions Targeted ultrasound can increase the density of VEGF105 cDNA in the area of myocardial ischemia, improve myocardial ischemia and reduce the area of myocardial infarction, promote the growth of microvascular.
出处
《中华超声影像学杂志》
CSCD
2005年第11期854-857,共4页
Chinese Journal of Ultrasonography
基金
上海市科委科研计划项目(034119870)
