摘要
目的心肌纤维化是心肌梗死后左室重构的主要组成部分,本实验主要观察骨髓基质干细胞移植对缺血性心肌左室重构细胞外基质的基因表达以及对心脏左室功能的影响。方法将骨髓基质干细胞经体外培养、5-氮杂胞苷(5-azacytidine)诱导、扩增及标记后,植入急性心肌梗死大鼠动物模型心肌中,于28d测定大鼠心脏功能后取出心脏并称量,对缺血性心肌的纤维化程度及注入的骨髓基质干细胞进行观察,应用逆转录聚合酶链反应(RT-PCR)及原位杂交技术,检测Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶1(MMP-1)和基质金属蛋白酶抑制剂1(TIMP-1)等细胞外基质基因表达情况,并观察了转化生长因子(TGF)-β1基因表达情况。结果在心肌中骨髓基质干细胞存活;梗死大鼠心脏功能明显改善;心肌梗死面积明显减小(10%);Ⅰ型胶原、Ⅲ型胶原、TIM-1以及TGF-β1基因表达水平与未注入骨髓基质干细胞对照组相比显著降低,且心肌细胞纤维化被有效抑制。结论骨髓基质干细胞移植可以抑制心肌纤维化,降低细胞外基质基因表达,改善心脏功能,有望成为心肌梗死治疗的一条新途径。
Objective Myocardial fibrosis is a major component of ventricular remodeling after myocardial infarction （M1） .The present study was to determine the outcome of bone marrow derived stem cell（MSC） transplantation into ischemic myocardium on left ventricular （LV） function, remodeling and extracellular matrix （ECM） gene expression. Methods We investigated the changes in collagen type Ⅰ , collagen type Ⅲ , matrix metalloproteinase （MMP）-Ⅰ, tissue inhibitor of matrix metalloproteinase（TIMP）-Ⅰ and in TGF-β1 mRNA expression by using reverse transcription polymerase chain reaction（RT-PCR） and in situ hybridization after Ml. Hemodynamic evaluations were performed at 28 days after coronary ligation. Results Heart/ body weight ratio in M1 ＋ MSC group decreased after ligation. However, LV systolic pressure （LVSP） and LV peak velocities of contraction and relaxation（ ＋ dP/dtmax and - dP/dtmax significantly increased compared with MI group（ P 〈 0.01）. Infarct size in M1 ＋ MSC group decreased by approximately 10% 28 days after MSC transplantation compared to M1 group. There were marked up-regulations of the mRNA expression of collagen type Ⅰ , collagen type Ⅲ ,TIMP-1 and TGF-βin MI rats, which was significantly attenuated by MSC transplantation. Conclusion MSC transplantation could inhibit LV remodeling, improve heart function and reduce extracellular matrix gene expression.
出处
《解剖学报》
CAS
CSCD
北大核心
2005年第4期376-380,共5页
Acta Anatomica Sinica
基金
国家自然科学基金资助项目(30170859)
关键词
心肌梗死
细胞移植
血液动力学
心脏功能
左室重构
大鼠
Myocardial infarction
Cell transplantation
Hemodynamics
Cardiac function
Remodeling
Rat
