PAMAM-D纳米载体介导TF反义寡脱氧核苷酸防治心肌缺血再灌注损伤的实验研究  

Experimental study on the preventive and therapeutic effects of polyamidoamine dendrimers mediated antisense oligodeoxynucleotide against tissue factor on myocardial ischemia-reperfusion injury in rats

作　　者：李春海[1] 桑翠玲[1] 宋树英[1] 张秀丽[1] 李新军[1] 李文慧[1] 尹俊[2] 

机构地区：[1]河北北方学院附属第二医院心内科,张家口市075100 [2]汕头大学医学院附属第二医院内科

出　　处：《河北医药》2011年第3期325-328,共4页Hebei Medical Journal

基　　金：河北省张家口市科技与地震局指导性计划(编号:1021108D)

摘　　要：目的研究聚酰胺-胺型树枝状高聚物(PAMAM-D)纳米载体介导组织因子(TF)反义寡脱氧核苷酸对大鼠心肌缺血再灌注损伤的作用。方法分别设计合成针对大鼠TF的反义寡脱氧核苷酸(AS/TF)、正义寡脱氧核苷酸(S/TF)和错配寡脱氧核苷酸(Sc/TF),将该三种寡脱氧核苷酸偶联于PAM-AM-D纳米载体,构建寡核苷酸-PAMAM-D的聚合物。将100只雄性Lewis大鼠随机等分为假手术组、缺血再灌注组、AS/TF防治组、S/TF对照组和Sc/TF对照组。结果心肌缺血90 min及再灌注3 h后,各组大鼠血液中的TnT和TAT均显著增多(与假手术组相比,P<0.05或<0.01),而AS/TF防治组大鼠血液中的TnT和TAT均明显低于其他3个缺血再灌注组(P<0.05或<0.01)。心肌缺血再灌注3 h后,缺血再灌注的各组大鼠梗死区及边缘区心肌组织中TF基因的转录和表达均强于假手术组(与假手术组相比,P<0.05或<0.01),而AS/TF防治组大鼠梗死区及边缘区心肌组织中TF基因的转录和表达则较其他3个缺血再灌注组明显减弱(P<0.01)。结论聚酰胺-胺型树枝状高聚物纳米载体介导的TF反义寡脱氧核苷酸对心肌缺血再灌注损伤有明显的保护作用。Objective To observe the effect of polyamidoamine dendrimers（PAMAM-D） mediated antisense oligodeoxynucleotide against tissue factor（TF） on myocardial ischemia-reperfusion injury in rats.Methods Antisense oligodeoxynucleotide against TF（AS/TF）,sense oligodeoxynucleotide against TF（S/TF） and scrambled oligodeoxynucleotide（Sc/TF） were designed and synthesized respectively,which were coupled with PAMAM-D nanometer vector and formed oligodeoxynucleotide-PAMAM-D polymer.100 male Lewis rats were randomly divided into sham operation group,ischemia-reperfusion group,AS/TF intervention group,S/TF control group and Sc/TF control group.Results 90 min after ischemia and at the end of reperfusion,the concentrations of TnT and TAT increased significantly（P0.05 or P 0.01）,as compared with those in sham operation group,however,the levels in AS/TF intervention group were much lower than those in the other 3 ischemia-reperfusion injury groups（P0.05 or P0.01）.After reperfusion,the transcription and expression of TF gene in myocardial cells of the infarction and ischemic zone were obviously enhanced in ischemia-reperfusion injury groups（P0.05 or P 0.01）,as compared with those in sham operation group,however,which were improved in AS/TF intervention group,as compared with those in the other 3 ischemia-reperfusion groups（P0.01）.Conclusion By antagonizing the transcription and expression of TF,polyamidoamine dendrimers nanometer vector mediated antisense oligodeoxynucleotide which has protective effect on myocardial ischemia-reperfusion injury.

关 键 词：聚酰胺-胺型树枝状高聚物 纳米载体 组织因子 反义寡脱氧核苷酸 心肌 缺血再灌注损伤 

分 类 号：R743.3[医药卫生—神经病学与精神病学]