Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Biomed Res Int. 2019 Jan 8;2019:5408289. doi: 10.1155/2019/5408289. eCollection 2019.
The present study was designed to further explore the role and the underlying molecular mechanism of phosphocreatine (PCr) for cardiac fibrosis . Isoproterenol (ISO) was used to induce cardiac fibrosis in rats. PCr administration ameliorated fibrosis by reducing collagen accumulation and fibrosis-related signals, including transforming growth factor beta 1 (TGF-1), alpha smooth muscle actin (-SMA), collagen type I, and collagen type III. Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-B) signaling pathways, including p38, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p65, were highly activated by ISO and blocked by PCr. Moreover, PCr decreased ISO-induced matrix metalloproteinase-9 (MMP-9) and increased the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. Furthermore, PCr suppressed cardiomyocyte apoptosis induced by ISO, as shown by downregulated expression of the proapoptotic caspase-3, Bax, and upregulated expression of the antiapoptotic Bcl-2. Taken together, PCr can be an effective agent for preventing cardiac fibrosis and cardiomyocyte apoptosis.
本研究旨在进一步探讨磷酸肌酸（PCr）在心脏纤维化中的作用及其潜在的分子机制。异丙肾上腺素（ISO）用于诱导大鼠心脏纤维化。PCr 给药通过减少胶原积累和纤维化相关信号（包括转化生长因子β 1（TGF-β1）、α平滑肌肌动蛋白（α-SMA）、I 型胶原和 III 型胶原）来改善纤维化。丝裂原激活的蛋白激酶（MAPKs）和核因子 kappa B（NF-κB）信号通路，包括 p38、细胞外信号调节激酶（ERK）、c-Jun N 末端激酶（JNK）和 p65，被 ISO 高度激活，并被 PCr 阻断。此外，PCr 降低 ISO 诱导的基质金属蛋白酶-9（MMP-9）的表达，增加组织金属蛋白酶抑制剂-1（TIMP-1）的表达。此外，PCr 抑制 ISO 诱导的心肌细胞凋亡，表现为促凋亡 caspase-3、Bax 的表达下调，抗凋亡 Bcl-2 的表达上调。综上所述，PCr 可能是预防心脏纤维化和心肌细胞凋亡的有效药物。
