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

作　　者：孔德松[1,2] 张自力[1,2] 雷娜[1,2] 张峰[1,2] 张晓平[1,2] 陆茵[1,2,3] 王爱云[1,2,3] 陈文星[1,2,3] 郑仕中[1,2,3] 

机构地区：[1]南京中医药大学药学院,江苏南京210029 [2]南京中医药大学中药学一级学科,江苏南京210046 [3]南京中医药大学江苏省中药药效与安全性评价重点实验室,江苏南京210046

出　　处：《中草药》2013年第1期70-75,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81270514;30873424);教育部博士点基金(20103237110010);江苏省自然科学基金资助项目(BK2008456);江苏省六大人才基金(2009-B-010);江苏省针灸学重点实验室开放课题(KJA200801);江苏高校优势学科建设工程资助项目(ysxk-2010);南京中医药大学中药学一级学科开放课题资助(2011ZYX4-008);十一五科技支撑计划(2008BAI51B02)

摘　　要：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.

关 键 词：姜黄素 肝纤维化 肝星状细胞 血小板衍生生长因子 细胞外基质 

分 类 号：R282.710.5[医药卫生—中药学]