超声介导微泡造影剂携带肝细胞生长因子基因靶向治疗大鼠急性心肌梗死  

Effects of hepatocyte growth factor gene transfer in combination with echocardiographic destruction of microbubbles in a rat model of experimental myocardial infarction

作　　者：丛阳[1] 方平[2] 王纯杰[1] 谭跃萍[2] 胡丹[2] 王磊[2] 

机构地区：[1]上海市普陀区人民医院超声诊断中心,200060 [2]第二军医大学第二附属长征医院康健苑超声检查室

出　　处：《中华心血管病杂志》2008年第10期936-939,共4页Chinese Journal of Cardiology

摘　　要：目的研究急性心肌梗死时超声介导微泡造影剂携带肝细胞生长因子（HGF）基因靶向治疗的可行性。方法将54只雄性SD大鼠建立心肌梗死模型并随机分成3组（每组18只）：US／MB—HGF组，予超声照射及尾静脉注射携带HGF质粒基因（pcDNA3.1-HGF）的微泡造影剂；US—HGF组，予超声照射及尾静脉注射pcDNA3．1-HGF。无微泡造影剂；US／MB-P组：即对照组，予超声照射及尾静脉注射携带空质粒的微泡造影剂。并按大鼠被处死的时间顺序，将每组分为3个亚组（每组6只）：24h组、7d组和14d组，分别取心肌组织做石蜡切片并做免疫组织化学染色，包括抗凋亡蛋白（bcl-2）的表达、HGF蛋白表达和CD34标记的毛细血管计数情况。结果（1）心肌组织HGF蛋白表达：US／MB—HGF7d亚组有明显的HGF蛋白表达，24h组未见有明显的HGF的表达颗粒。US—HGF7d和14d亚组可见少量HGF表达。US／MB—P组各亚组均未见HGF表达。（2）CD34标记的毛细血管计数：US／MB-HGF14d亚组为（367．6±17．6）个／高倍视野，明显高于US-HGF组[（268．9±0．8）个／高倍视野]和US／MB—P组[（186．8±11．8）个／高倍视野，均P〈0．05]，各组24h和7d亚组的毛细血管计数均低于其14d亚组。（3）梗死区bcl-2的表达：US／MB—HGF7d亚组为9．9％±0．5％，明显高于US—HGF组（6．3％±1．0％）和US／MB—P组（3．5％±0．8％，均P〈0．05）；US／MB—HGF14d亚组为6．7％±0．9％，明显高于US．HGF组（4．5％±0．8％）和US／MB—P组（2．1％±0．9％，均P〈0．05）；3组24h亚组均未见明显表达。结论超声介导造影剂微泡破裂可以使静脉注射的HGF基因在心肌局部浓度增高，增强其转染和表达，且可明显促进心肌新生血管的生长，减少急性梗死区心肌细胞的凋亡。Objective To evaluate whether ultrasonic microbubble destruction （US/MB） could enhance the therapeutic effects of hepatocyte growth factor （HGF） gene transfer for acute myocardial infarction （MI）. Methods MI was induced by left anterior descending artery ligation in male SD rats. Two to 4 hours thereafter, MI rats were randomly treated with tail vein infusing pc-DNA3.1-HGF plasmid mixed with microbubbles （US/MB-HGF group, n = 18 ） ; tail vein infusing pc-DNA3.1-HGF plasmid mixed with saline （ US-HGF group, n = 18） ; tail vein infusing empty plasmid mixed with microbubbles （ US/MB-P group, n = 18）. All rats were exposed to ultrasound treatment thereafter till contrast imaging disappeared in cardiac region. Rats were sacrificed at 24 hours, 7 days or 14 days, respectively （ n = 6 each） and myocardial protein expression of bcl-2 and HGF as well as microvascular density （MVD） were determined. Results The myocardial protein expressions of bcl-2 and HGF in US/MB-HGF group were significantly higher than those in US-HGF and US/MB-P groups at 7 days post MI （ all P 〈0.01 ） and MVD was significandy higher in US/MB-HGF group （367.6± 17. 6） than that in US-HGF （268.9 ±0. 8） and US/MB-P （ 186. 8 ± 11.8） groups （ all P 〈 0. 05 ） at 14 days post MI. Conclusions Ultrasound-mediated microbubble destruction could enhance systemic HGF administration induced myocardial angiogenesis and reduce systemic HGF administration induced myocardial apoptosis in rats with acute MI.

关 键 词：心肌梗死 超声心动描记术 基因 治疗学 

分 类 号：R686[医药卫生—骨科学]