Wang Jian-an, Luo Rong-hua, Zhang Xing, Xie Xiao-jie, Hu Xin-yang, He Ai-na, Chen Jie, Li Jia-hui
Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
J Zhejiang Univ Sci B. 2006 Aug;7(8):641-7. doi: 10.1631/jzus.2006.B0641.
This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction.
Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis.
The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups.
Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.
本研究旨在从分子机制方面评估与血管紧张素转换酶抑制剂(ACEI)培哚普利相比,间充质干细胞(MSC)植入对急性心肌梗死后缺血心肌左心室重构的影响。
40只大鼠分为四组:对照组、MSC组、ACEI组、MSC + ACEI组。在MSC组和MSC + ACEI组中,将骨髓干细胞来源的大鼠立即注射到冠状动脉结扎造成缺血的区域。对照组注射磷酸盐缓冲盐水(PBS)。ACEI组和MSC + ACEI组经口给予培哚普利。植入6周后,处死大鼠并采集心脏样本。采用改良的Masson三色染色法观察纤维状胶原。采用蛋白质免疫印迹法评估梗死区基质金属蛋白酶(MMP)-2、基质金属蛋白酶(MMP)-9的蛋白表达。通过逆转录聚合酶链反应(RT-PCR)分析检测梗死区MMP2、MMP9和基质金属蛋白酶组织抑制剂(TIMP)-1的转录水平。
MSC组、ACEI组和MSC + ACEI组梗死区的纤维状胶原面积、MMP2、MMP9的蛋白表达以及MMP2、MMP9 mRNA的转录水平均降低。四组间TIMP1 mRNA表达无显著差异。
MSC和ACEI均可通过改变胶原代谢减少梗死区重构。