腦鈉素和心電圖評(píng)價(jià)細(xì)胞移植治療急性心肌梗死的實(shí)驗(yàn)研究.pdf
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·基礎(chǔ)研究·
收稿日期: 2007 - 03 - 02
基金項(xiàng)目: 國(guó)家自然科學(xué)基金資助項(xiàng)目(30471719) ;上海市教委曙光計(jì)劃(04SG25) ;上海市浦東新區(qū)優(yōu)秀學(xué)科帶頭人項(xiàng)目(PWR2004 - 1)
作者簡(jiǎn)介: 汪進(jìn)益(1974 - ) ,男,博士. E2mail : Jinyi
-
wang @126. com
通訊作者: 劉中民. E2mail : zhongmin
-
liu @sina. com
腦鈉素和心電圖評(píng)價(jià)細(xì)胞移植治療
急性心肌梗死的實(shí)驗(yàn)研究
汪進(jìn)益1
, 范慧敏1
, 劉中民1
, 張旭敏1
, 馬 亮2
, 李 楊2
(1. 同濟(jì)大學(xué)附屬東方醫(yī)院心胸外科,上海 200120 ; 2. 同濟(jì)大學(xué)附屬東方醫(yī)院細(xì)胞治療室,上海 200120)
【摘要】目的 探討肌肉轉(zhuǎn)錄調(diào)節(jié)因子(myogenic determination , MyoD)基因和連接蛋白 43 (connexin 43 , Cx43)基
因體外共轉(zhuǎn)染大鼠皮膚真皮成纖維細(xì)胞(dermal fibroblasts , DFs)后在心肌梗死部位原位移植修復(fù)梗死心肌組織的
近期療效及其安全性。方法 60 只 SD雄性大鼠隨機(jī)分成 4 組( n = 15) 。正常對(duì)照組: 取 100μl 細(xì)胞培養(yǎng)液基質(zhì)
植入到正常心肌組織中;心梗對(duì)照組: 取等量細(xì)胞培養(yǎng)液基質(zhì)植入到心肌梗死大鼠瘢痕組織中;正常移植組: 在正
常心肌組織中植入等量用5 - 溴脫氧尿嘧啶核苷(BrdU)標(biāo)記經(jīng) MyoD和 Cx43 基因聯(lián)合轉(zhuǎn)染DFs細(xì)胞懸液;心梗移
植組: 在心梗后瘢痕組織中植入等量同樣的細(xì)胞懸液 ,細(xì)胞密度均為 2. 0 ×106
/ ml。在細(xì)胞移植前、移植后 4 周內(nèi)
動(dòng)態(tài)監(jiān)測(cè)心電圖和血漿腦鈉肽(B2type nat riuretic peptide , BNP)水平的變化。結(jié)果 心梗對(duì)照組和心梗移植組血漿
BNP濃度較正常對(duì)照組和正常移植組明顯升高( P < 0. 01) ;心梗移植組較心梗對(duì)照組血漿BNP濃度在術(shù)后 1 d、 1
周及 2 周無差異 ,在 4 周后明顯降低( P < 0. 01) 。心梗大鼠 Ⅱ?qū)?lián)心電圖的 QRS波增寬 ,ST段、 T波抬高;細(xì)胞移
植早期 ST段、 T波快速回落 ,2 周內(nèi)回落大于 50 %;4周后正常移植組和心梗移植組大鼠均未見致命性心律失常 ,且心梗移植組與心梗對(duì)照組(或移植前)相比 QRS波變窄 ,R波相對(duì)升高 ,ST段回到基線。結(jié)論 用 MyoD和 Cx43
基因轉(zhuǎn)染DFs后原位心肌移植 ,可以降低血漿BNP水平和改善心電圖 ,兩者的動(dòng)態(tài)監(jiān)測(cè)為評(píng)價(jià)細(xì)胞移植治療急性
心梗提供了有效實(shí)用的方法。
【關(guān)鍵詞】腦鈉素; 心電圖; 急性心肌梗死; 細(xì)胞移植; 大鼠
【中圖分類號(hào)】R 542. 22 【文獻(xiàn)標(biāo)識(shí)碼】A 【文章編號(hào)】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 濟(jì) 大 學(xué) 學(xué) 報(bào) ( 醫(yī) 學(xué) 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
基金項(xiàng)目: 國(guó)家自然科學(xué)基金資助項(xiàng)目(30471719) ;上海市教委曙光計(jì)劃(04SG25) ;上海市浦東新區(qū)優(yōu)秀學(xué)科帶頭人項(xiàng)目(PWR2004 - 1)
作者簡(jiǎn)介: 汪進(jìn)益(1974 - ) ,男,博士. E2mail : Jinyi
-
wang @126. com
通訊作者: 劉中民. E2mail : zhongmin
-
liu @sina. com
腦鈉素和心電圖評(píng)價(jià)細(xì)胞移植治療
急性心肌梗死的實(shí)驗(yàn)研究
汪進(jìn)益1
, 范慧敏1
, 劉中民1
, 張旭敏1
, 馬 亮2
, 李 楊2
(1. 同濟(jì)大學(xué)附屬東方醫(yī)院心胸外科,上海 200120 ; 2. 同濟(jì)大學(xué)附屬東方醫(yī)院細(xì)胞治療室,上海 200120)
【摘要】目的 探討肌肉轉(zhuǎn)錄調(diào)節(jié)因子(myogenic determination , MyoD)基因和連接蛋白 43 (connexin 43 , Cx43)基
因體外共轉(zhuǎn)染大鼠皮膚真皮成纖維細(xì)胞(dermal fibroblasts , DFs)后在心肌梗死部位原位移植修復(fù)梗死心肌組織的
近期療效及其安全性。方法 60 只 SD雄性大鼠隨機(jī)分成 4 組( n = 15) 。正常對(duì)照組: 取 100μl 細(xì)胞培養(yǎng)液基質(zhì)
植入到正常心肌組織中;心梗對(duì)照組: 取等量細(xì)胞培養(yǎng)液基質(zhì)植入到心肌梗死大鼠瘢痕組織中;正常移植組: 在正
常心肌組織中植入等量用5 - 溴脫氧尿嘧啶核苷(BrdU)標(biāo)記經(jīng) MyoD和 Cx43 基因聯(lián)合轉(zhuǎn)染DFs細(xì)胞懸液;心梗移
植組: 在心梗后瘢痕組織中植入等量同樣的細(xì)胞懸液 ,細(xì)胞密度均為 2. 0 ×106
/ ml。在細(xì)胞移植前、移植后 4 周內(nèi)
動(dòng)態(tài)監(jiān)測(cè)心電圖和血漿腦鈉肽(B2type nat riuretic peptide , BNP)水平的變化。結(jié)果 心梗對(duì)照組和心梗移植組血漿
BNP濃度較正常對(duì)照組和正常移植組明顯升高( P < 0. 01) ;心梗移植組較心梗對(duì)照組血漿BNP濃度在術(shù)后 1 d、 1
周及 2 周無差異 ,在 4 周后明顯降低( P < 0. 01) 。心梗大鼠 Ⅱ?qū)?lián)心電圖的 QRS波增寬 ,ST段、 T波抬高;細(xì)胞移
植早期 ST段、 T波快速回落 ,2 周內(nèi)回落大于 50 %;4周后正常移植組和心梗移植組大鼠均未見致命性心律失常 ,且心梗移植組與心梗對(duì)照組(或移植前)相比 QRS波變窄 ,R波相對(duì)升高 ,ST段回到基線。結(jié)論 用 MyoD和 Cx43
基因轉(zhuǎn)染DFs后原位心肌移植 ,可以降低血漿BNP水平和改善心電圖 ,兩者的動(dòng)態(tài)監(jiān)測(cè)為評(píng)價(jià)細(xì)胞移植治療急性
心梗提供了有效實(shí)用的方法。
【關(guān)鍵詞】腦鈉素; 心電圖; 急性心肌梗死; 細(xì)胞移植; 大鼠
【中圖分類號(hào)】R 542. 22 【文獻(xiàn)標(biāo)識(shí)碼】A 【文章編號(hào)】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 濟(jì) 大 學(xué) 學(xué) 報(bào) ( 醫(yī) 學(xué) 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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