摘要
目的探讨肌肉转录调节因子(myogenic determination,MyoD)基因和连接蛋白43(connexin 43,Cx43)基因体外共转染大鼠皮肤真皮成纤维细胞(dermal fibroblasts,DFs)后在心肌梗死部位原位移植修复梗死心肌组织的近期疗效及其安全性。方法60只SD雄性大鼠随机分成4组(n=15)。正常对照组:取100μl细胞培养液基质植入到正常心肌组织中;心梗对照组:取等量细胞培养液基质植入到心肌梗死大鼠瘢痕组织中;正常移植组:在正常心肌组织中植入等量用5-溴脱氧尿嘧啶核苷(BrdU)标记经MyoD和Cx43基因联合转染DFs细胞悬液;心梗移植组:在心梗后瘢痕组织中植入等量同样的细胞悬液,细胞密度均为2.0×106/ml。在细胞移植前、移植后4周内动态监测心电图和血浆脑钠肽(B-type natriuretic peptide,BNP)水平的变化。结果心梗对照组和心梗移植组血浆BNP浓度较正常对照组和正常移植组明显升高(P<0.01);心梗移植组较心梗对照组血浆BNP浓度在术后1 d、1周及2周无差异,在4周后明显降低(P<0.01)。心梗大鼠Ⅱ导联心电图的QRS波增宽,ST段、T波抬高;细胞移植早期ST段、T波快速回落,2周内回落大于50%;4周后正常移植组和心梗移植组大鼠均未见致命性心律失常,且心梗移植组与心梗对照组(或移植前)相比QRS波变窄,R波相对升高,ST段回到基线。结论用MyoD和Cx43基因转染DFs后原位心肌移植,可以降低血浆BNP水平和改善心电图,两者的动态监测为评价细胞移植治疗急性心梗提供了有效实用的方法。
Objective To investigate the efficacy and safety of dermal fibroblasts （DFs） of transplantation in situ at myocardium infarct sites for repairing infarct myocardium in rats after acute myocardial infarction （AMI）, after the DFs were transfeeted by both myogenic transcription factor-myogenic determination （MyoD） gene and gap junctions protein-cormexin43 （Cx43） gene. Methods Sixty male Sprague-Dawley （SD） rats were randomly divided into 4 groups, normal control group： 100 μl cell culture mediums were injected into the normal myocardial tissues, myocardial infarction control group： 100 μl cell culture mediums were injected into the scar tissues of the myocardial infarction rats. normal transplantation group： 100 μl cell suspension of MyoD/ Cx43-converted DFs （2.0 × 10^6 cells/ml） which labeled by bromodeoxyuridine （BrdU） were injected into the normal myocardial tissues, myocardial infarction transplantation group： 100 μl cell suspension of MyoD/Cx43- converted DFs （2.0×10^6 cells/ml） with BrdU labeled were injected into the scar tissues after myocardial infarction. The changes of dynamic electrocardiogram （ECG） and plasma B-type natriuretic peptide （BNP） concentration were measured before and 4 weeks after operation of cell transplantation. Results After MyoD/ Cx4 3- converted DFs were transplanted into normal myocardial tissue and scar tissue, plasma BNP concentration in myocardial infarction control group and myocardial infarction transplantation group were higher than those in normal control group and normal transplantation group （P 〈 0.01 ）, and plasma BNP concentration in myocardial infarction control group were higher than those in myocardial infarction transplantation group after 4 weeks （P 〈 0.01）. QRS of lead II wave was broadened and ST segment shifted up in the AMI rat models. The fall of ST segment and T wave was more than 50% within 2 weeks after cell transplantation. There was no serious arrhythmia in both normal transplantation group an
出处
《同济大学学报（医学版）》
CAS
2008年第1期21-24,33,共5页
Journal of Tongji University(Medical Science)
基金
国家自然科学基金资助项目(30471719)
上海市教委曙光计划项目(04SG25)
上海市浦东新区优秀学科带头人项目(PWR2004-1)
关键词
脑钠素
心电图
急性心肌梗死
细胞移植
大鼠
B-type natriuretic peptide
electrocardiogram
acute myocardial infarction
cellular transplantation
rat
