姜黄素对血小板衍生生长因子诱导活化的肝星状细胞细胞外基质的影响

Effects of curcumin on extracellular matrix in hepatic stellate cells activated by platelet-derived growth factor

目的研究姜黄素对血小板衍生生长因子(PDGF)诱导活化的肝星状细胞细胞外基质沉积的干预机制。方法以Western blotting和RT-PCR方法分别检测姜黄素对PDGF诱导活化的肝星状细胞中α-平滑肌肌动蛋白(α-SMA)、细胞外基质主要成分I型前胶原(α1I胶原)和纤黏蛋白的表达,以及对调控细胞外基质降解平衡的基质金属蛋白酶(MMP)-2、MMP-9与其组织抑制剂(TIMP-1)蛋白与mRNA表达的影响。结果姜黄素可显著下调α-SMA、α1I胶原和纤黏蛋白的蛋白与mRNA表达,减少细胞外基质的沉积;还可调节细胞外基质的降解平衡,表现为TIMP-1表达下调和MMP-2的表达上调。结论姜黄素能够抑制PDGF诱导的肝星状细胞合成与分泌细胞外基质增加,促进细胞外基质降解,减少细胞外基质在肝脏中的沉积,进而发挥治疗肝纤维化的作用。

Objective To investigate the effects of curcumin on extracellular matrix deposition in hepatic stellate cells （HSCs） activated by platelet-derived growth factor （PDGF） and to elucidate the underlying mechanisms. Methods Western blotting and RT-PCR were used to detect the expression of or-smooth muscle actin （α-SMA）, main constituents in extracellular matrix I procollagen （αlI collagen）, and fibronectin in PDGF-stimulated HSCs, and to observe the effects on the expression of matrix metalloproteinase （MMP）-2, MMP-9, and TIMP-1 protein and mRNA related to regulate the degradation balance in extracellular matrix. Results Curcumin could obviously reduce the expression of α-SMA, αlI collagen, and fibronectin at both protein and mRNA levels and reduce the deposition of extracellular matrix. Moreover, curcumin could also regulate the degradation balance through the down-regulation of TIMP- 1 expression while the up-regulation MMP-2 expression. Conclusion Curcumin could inhibit the synthesis and secretion of extracellular matrix of HSCs activated by PDGF, promote the degradation of extracellular matrix, decrease the deposition of extracellular matrix in liver, and therefore show the therapeutical effects on hepatic fibrosis.