Du You-you, Yao Rui, Pu Shi, Zhao Xiao-yan, Liu Guang-hui, Zhao Luo-sha, Chen Qing-hua, Li Ling
Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2012 Dec;40(12):1045-50.
To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI).
MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-β(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot.
(1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-β(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05).
MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-β(1)-Smad2 signaling pathway in this model.
探讨间充质干细胞(MSC)植入对心肌梗死(MI)后梗死区域聚集的肌成纤维细胞的调节作用。
通过结扎左冠状动脉前降支诱导SD大鼠发生MI,将实验动物随机分为假手术组、MI + PBS组和MI + MSC组(在梗死区域四个部位心肌注射0.1 ml 2×10(7)/ml)。进行超声心动图、血流动力学检查和Masson三色染色。通过免疫荧光染色研究植入的MSC分化及梗死区域聚集的肌成纤维细胞。采用实时RT-PCR和Western blot检测TGF-β(1)-Smad2信号通路。
(1)四周后,MI + MSC组的心脏重量/体重比[(3.04 ± 0.16)mg/g vs.(3.34 ± 0.14)mg/g,P < 0.01]和心肌梗死面积[(38.72 ± 2.38)% vs.(46.36 ± 2.81)%,P < 0.01]均显著低于MI + PBS组,而MI + MSC组梗死区域的瘢痕厚度更厚[(0.93 ± 0.17)mm vs.(0.65 ± 0.16)mm,P = 0.01],左室射血分数更高[左室射血分数:(32.5 ± 5.9)% vs.(26.5 ± 4.5)%,P = 0.03]。(2)与MI + PBS组相比,MI + MSC组梗死区域聚集的肌成纤维细胞显著增多[(196 ± 20)个细胞/mm(2) vs.(89 ± 25)个细胞/mm(2),P < 0.01],且部分植入的MSC表达α-SMA(+)。(3)与MI + PBS组相比,MI + MSC组梗死区域TGF-β(1)表达及Smad2磷酸化水平均显著上调(均P < 0.05)。
在该模型中,MSC可通过激活TGF-β(1)-Smad2信号通路改善心肌功能并促进梗死区域肌成纤维细胞聚集。