声动力疗法抑制转化生长因子-β1诱导的大鼠心脏成纤维细胞纤维化。
Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1.
作者信息
Guo Yuanyuan, Dong Zengxiang, Shi Yuanqi, Wang Wei, Wang Lu, Sun Jing, Sun Xin, Tian Zhen, Yao Jianting, Li Zhitao, Cheng Jiali, Tian Ye
机构信息
Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.
出版信息
Cell Physiol Biochem. 2016;40(3-4):579-588. doi: 10.1159/000452571. Epub 2016 Nov 25.
BACKGROUND/AIMS: Sonodynamic therapy (SDT) is a localized ultrasound-activated therapy for atherosclerosis when combined with a sonosensitizer, 5-aminolevulinic acid (ALA), but whether it can prevent cardiac fibrosis has not been studied. In the present study, we evaluated the effects SDT on fibrogenesis in rat cardiac fibroblasts.
METHODS
The primary cardiac fibroblasts were isolated from rats, and induced to fibrogenesis with TGF-β1. With this in vitro model, we tested the preventive effects of SDT on fibrogenesis and further the underlying mechanism.
RESULTS
TGF-β1 stimulation up-regulated α-SMA and COLI/III protein levels in cardiac fibroblasts, and enhanced the progression of cells from the G0/G1 phase to the S phase. SDT inhibited the TGF-β1 mediated cell proliferation and decreased the levels of α-SMA and COLI/III by activating AKT/GSK3β pathway and blocking TGF-β1/SMAD3 signaling.
CONCLUSION
Our studies demonstrate an antifibrotic effect of SDT in rat cardiac fibroblasts, suggesting that SDT may intervene cardiac fibrogenesis by regulating myocardial fibrotic remodeling.
背景/目的：声动力疗法（SDT）是一种与声敏剂5-氨基乙酰丙酸（ALA）联合应用于动脉粥样硬化的局部超声激活疗法，但它是否能预防心脏纤维化尚未见研究报道。在本研究中，我们评估了SDT对大鼠心脏成纤维细胞纤维化形成的影响。
方法
从大鼠分离出原代心脏成纤维细胞，并用转化生长因子-β1（TGF-β1）诱导其纤维化形成。利用该体外模型，我们测试了SDT对纤维化形成的预防作用及其潜在机制。
结果
TGF-β1刺激上调了心脏成纤维细胞中α-平滑肌肌动蛋白（α-SMA）和Ⅰ型/Ⅲ型胶原蛋白（COLI/III）蛋白水平，并促进细胞从G0/G1期进入S期。SDT通过激活AKT/糖原合成酶激酶3β（GSK3β）信号通路和阻断TGF-β1/信号转导分子3（SMAD3）信号，抑制TGF-β1介导的细胞增殖，并降低α-SMA和COLI/III水平。
结论
我们的研究证明了SDT在大鼠心脏成纤维细胞中具有抗纤维化作用，提示SDT可能通过调节心肌纤维化重塑来干预心脏纤维化形成。
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