Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction
Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction
复制标题
DOI：
10.1093/abbs/gmr087
复制
发表时间：
2011-11-01
影响因子：
3.7
通讯作者：
Mai, Weiyi
中科院分区：
文献类型：
--
作者：
Cai, Anping;Zheng, Dongdan;Mai, Weiyi
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）已被广泛应用于急性心肌梗死（acute myocardial infarction，AMI）后心肌细胞损伤的修复。然而，MSCs在缺血性心脏病中的最佳治疗效果受到其存活率低和分化率低的阻碍。因此，提高MSC的存活率和分化率是保证MSC在AMI中的疗效的关键。本文将从大鼠腹股沟脂肪组织中分离的间充质干细胞命名为脂肪间充质干细胞（adipose-derived mesenchymal stem cells，ASCs），并将第4代ASCs与心肌细胞共培养，命名为co-ASCs。14 d后，用细胞免疫荧光法检测加塔-4（一种转录因子）和心肌肌钙蛋白-I。在大鼠AMI后的前24 h内给予阿托伐他汀（Ator组）或溶剂（对照组）。14天后，评价炎症参数和心功能。对其他存活大鼠注射总共1 × 10（6）co-ASC/100 μ l磷酸盐缓冲盐水（PBS）、1 × 10（6）ASC/100 μ l PBS或100 μ l PBS。细胞注射后28天，评估移植细胞的存活率和分化率以及心脏功能。在co-ASC中，加塔-4表达的百分比为28.5% +/- 5.6%，心肌肌钙蛋白-I为22.8% +/-3.2%。与对照组相比，Ator 3个剂量组的心肌浸润炎细胞数、髓过氧化物酶活性、炎性细胞因子（VCAM-1、TNF-α、Hs-CRP）mRNA表达及Bax蛋白表达均明显减少，Bcl-2蛋白表达及心功能均明显改善（P < 0.05）。与Ator 2 + ASCs组和Con + co-ASCs组相比，Ator 3 + co-ASCs组移植的4-6-diamidino-2-phenylindole染色细胞数和心肌肌钙蛋白I阳性细胞数以及心功能改善最为显著（P < 0.05）。预先改善心脏环境，结合预先指定ASC，有利于提高ASC对AMI后心功能的治疗效果。
Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 x 10(6) co-ASCs/100 mu l phosphate-buffered saline (PBS), 1 x 10(6) ASCs/100 mu l PBS, or 100 mu l PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% +/- 5.6% and of cardiac troponin-I was 22.8% +/- 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-alpha, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P < 0.05). Compared with the Ator2 + ASCs group and Con + co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 + co-ASCs group (P < 0.05). Pre-amelioration of the cardiac milieu, in conjunction with pre-specification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI.