脑钠素和心电图评价细胞移植治疗急性心肌梗死的实验研究.pdf
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·基础研究·
收稿日期: 2007 - 03 - 02
基金项目: 国家自然科学基金资助项目(30471719) ;上海市教委曙光计划(04SG25) ;上海市浦东新区优秀学科带头人项目(PWR2004 - 1)
作者简介: 汪进益(1974 - ) ,男,博士. E2mail : Jinyi
-
wang @126. com
通讯作者: 刘中民. E2mail : zhongmin
-
liu @sina. com
脑钠素和心电图评价细胞移植治疗
急性心肌梗死的实验研究
汪进益1
, 范慧敏1
, 刘中民1
, 张旭敏1
, 马 亮2
, 李 杨2
(1. 同济大学附属东方医院心胸外科,上海 200120 ; 2. 同济大学附属东方医院细胞治疗室,上海 200120)
【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(B2type nat riuretic 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。
【关键词】脑钠素; 心电图; 急性心肌梗死; 细胞移植; 大鼠
【中图分类号】R 542. 22 【文献标识码】A 【文章编号】1008 - 0392 (2008) 01 - 0021 - 04
Assessment of therapeutic effect and safety by dynamic monitoring B 2type
natriuretic peptide and electrocardiogram during perioperation of
cellular transplantation for acute myocardial infarction rats
WA N G Jin2yi
1
, FA N Hui2min
1
, L IU Zhong2min
1
,ZHA N G XU2min
1
, Ma L iang
2
, L I Yang
2
(1. Dept . of Cardiovascular and Thoracic Surgery , East Hospital , Tongji University , Shanghai 200120 , China ;
2. Dept . of Cell Treatment Centre , East Hospital , Tongji University , Shanghai 200120 , China)
【Abstract】Objective To investigate the efficacy and safety of dermal fibroblasts (DFs) of t ransplantation in
situ at myocardium infarct sites for repairing infarct myocardium in rats after acute myocardial infarction
· 12 ·
第29 卷第1 期
2008 年2 月
同 济 大 学 学 报 ( 医 学 版 )
JOURNAL OF TONGJ I UNIVERSITY (MEDICAL SCIENCE)
Vol . 28 No. 1
Feb. , 2008(AMI) , after the DFs were t ransfected by both myogenic t ranscription factor2 2myogenic determination (My2
oD) gene and gap junctions protein2connexin43 (Cx43) gene. Methods Sixty male Sprague2Dawley (SD) rats
were randomly divided into 4 groups. normal cont rol group : 100μ l cell culture mediums were injected into the
normal myocardial tissues. myocardial infarction cont rol group : 100μ l cell culture mediums were injected into
the scar tissues of the myocardial infarction rats. normal t rans plantation group : 100μ l cell suspension of MyoD/
Cx432converted DFs (2. 0 ×106
cells/ ml) which labeled by bromodeoxyuridine (BrdU) were injected into the
normal myocardial tissues. myocardial infarction t ransplantation group : 100μ l cell suspension of MyoD/ Cx432
converted DFs (2. 0 ×106
cells/ ml) with BrdU labeled were injected into the scar tissues after myocardial in2
farction. The changes of dynamic elect rocardiogram ( ECG) and plasma B2type nat riuretic peptide (BNP) con2
cent ration were measured before and 4 weeks after operation of cell t ransplantation. Results After MyoD/ ......
收稿日期: 2007 - 03 - 02
基金项目: 国家自然科学基金资助项目(30471719) ;上海市教委曙光计划(04SG25) ;上海市浦东新区优秀学科带头人项目(PWR2004 - 1)
作者简介: 汪进益(1974 - ) ,男,博士. E2mail : Jinyi
-
wang @126. com
通讯作者: 刘中民. E2mail : zhongmin
-
liu @sina. com
脑钠素和心电图评价细胞移植治疗
急性心肌梗死的实验研究
汪进益1
, 范慧敏1
, 刘中民1
, 张旭敏1
, 马 亮2
, 李 杨2
(1. 同济大学附属东方医院心胸外科,上海 200120 ; 2. 同济大学附属东方医院细胞治疗室,上海 200120)
【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(B2type nat riuretic 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。
【关键词】脑钠素; 心电图; 急性心肌梗死; 细胞移植; 大鼠
【中图分类号】R 542. 22 【文献标识码】A 【文章编号】1008 - 0392 (2008) 01 - 0021 - 04
Assessment of therapeutic effect and safety by dynamic monitoring B 2type
natriuretic peptide and electrocardiogram during perioperation of
cellular transplantation for acute myocardial infarction rats
WA N G Jin2yi
1
, FA N Hui2min
1
, L IU Zhong2min
1
,ZHA N G XU2min
1
, Ma L iang
2
, L I Yang
2
(1. Dept . of Cardiovascular and Thoracic Surgery , East Hospital , Tongji University , Shanghai 200120 , China ;
2. Dept . of Cell Treatment Centre , East Hospital , Tongji University , Shanghai 200120 , China)
【Abstract】Objective To investigate the efficacy and safety of dermal fibroblasts (DFs) of t ransplantation in
situ at myocardium infarct sites for repairing infarct myocardium in rats after acute myocardial infarction
· 12 ·
第29 卷第1 期
2008 年2 月
同 济 大 学 学 报 ( 医 学 版 )
JOURNAL OF TONGJ I UNIVERSITY (MEDICAL SCIENCE)
Vol . 28 No. 1
Feb. , 2008(AMI) , after the DFs were t ransfected by both myogenic t ranscription factor2 2myogenic determination (My2
oD) gene and gap junctions protein2connexin43 (Cx43) gene. Methods Sixty male Sprague2Dawley (SD) rats
were randomly divided into 4 groups. normal cont rol group : 100μ l cell culture mediums were injected into the
normal myocardial tissues. myocardial infarction cont rol group : 100μ l cell culture mediums were injected into
the scar tissues of the myocardial infarction rats. normal t rans plantation group : 100μ l cell suspension of MyoD/
Cx432converted DFs (2. 0 ×106
cells/ ml) which labeled by bromodeoxyuridine (BrdU) were injected into the
normal myocardial tissues. myocardial infarction t ransplantation group : 100μ l cell suspension of MyoD/ Cx432
converted DFs (2. 0 ×106
cells/ ml) with BrdU labeled were injected into the scar tissues after myocardial in2
farction. The changes of dynamic elect rocardiogram ( ECG) and plasma B2type nat riuretic peptide (BNP) con2
cent ration were measured before and 4 weeks after operation of cell t ransplantation. Results After MyoD/ ......
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