Institute of Medicine, Qiqihar Medical University, China.
Am J Chin Med. 2012;40(3):481-94. doi: 10.1142/S0192415X12500371.
Hepatic stellate cells (HSCs) undergo activation during the development of liver fibrosis. Transcription factor myocyte enhancer factor (MEF2) 2C plays a key role in this process. In the present study, we investigated the effect of hydroxysafflor yellow A (HSYA) on hepatic fibrosis and further investigated potential mechanisms in vivo. Sprague-Dawley rats were administered with CCl(4) together with or without HYSA for 12 weeks. The effect of HYSA on hepatic fibrosis was evaluated using hematoxylin-eosin and Van Gieson staining. Messenger RNA expression was quantified by real-time polymerase chain reaction, and protein was quantified by Western blot or immunohistochemistry. Our results revealed that CCl(4) treatment induced micronodular hepatic fibrosis with a pronounced deposition of collagen fibers. Treatment with HYSA resulted in a significant decrease in fibrosis, protein expression of α-SMA, and MEF-2C gene expression. This was accompanied by a decreased expression of Tβ-RI, Tβ-RII, MEKK3, MEK5, and phosphorylation of ERk5. HYSA alone had no effect on the measured parameters. Our findings demonstrate that HSYA protected, at least in part, the rat liver from CCl(4)-caused fibrogenesis through inhibition of hepatic stellate cell (HSC) activation, attenuation of transforming growth factor beta (TGF-β) signaling. HSYA may become a novel and promising agent for the inhibition of hepatic fibrosis.
肝星状细胞（HSCs）在肝纤维化的发展过程中发生激活。转录因子肌细胞增强因子 2C（MEF2）2C 在这一过程中发挥关键作用。在本研究中，我们研究了羟基红花黄色素 A（HSYA）对肝纤维化的影响，并进一步在体内研究了潜在的机制。SD 大鼠给予 CCl4 同时或不给予 HSYA 共 12 周。通过苏木精-伊红和 Van Gieson 染色评估 HSYA 对肝纤维化的影响。通过实时聚合酶链反应定量信使 RNA 表达，通过 Western blot 或免疫组织化学定量蛋白质。我们的结果表明，CCl4 处理诱导微结节性肝纤维化，伴有明显的胶原纤维沉积。HSYA 处理导致纤维化、α-SMA 蛋白表达和 MEF-2C 基因表达显著减少。这伴随着 Tβ-RI、Tβ-RII、MEKK3、MEK5 和 ERk5 磷酸化的减少。HSYA 单独对所测量的参数没有影响。我们的研究结果表明，HSYA 通过抑制肝星状细胞（HSC）激活、减弱转化生长因子-β（TGF-β）信号，至少部分保护大鼠肝脏免受 CCl4 引起的纤维化。HSYA 可能成为抑制肝纤维化的一种新的有前途的药物。
