姜黄素激活过氧化物酶体增殖因子活化受体γ信号对大鼠肝星状细胞基质金属蛋白酶2、9活性和胞核核因子-κBp65表达的影响

Effect of Curcumin on Activity of Matrix Metalloproteinase 2,9 and Nuclear Expression of RelA in Rat Hepatic Stellate Cells by Activating Peroxisome Proliferator-activated Receptor γ Signal

免费下载全文查看/发表评论下载PDF阅读器

DOI：

中文关键词: 姜黄素过氧化物酶体增殖因子活化受体γ 细胞基质金属蛋白酶核因子-κBp65

英文关键词:curcumin peroxisome proliferator-activated receptor γ matrix metalloproteinases RelA

基金项目:国家自然科学基金项目(No.30300458)

作者	单位
成扬	上海中医药大学附属曙光医院肝病研究所上海201203
平键	上海中医药大学附属曙光医院肝病研究所上海201203
刘成	上海中医药大学附属曙光医院肝病研究所上海201203
徐列明	上海中医药大学附属曙光医院肝病研究所上海201203

摘要点击次数: 1319

全文下载次数: 3

中文摘要:

目的研究姜黄素激活过氧化物酶体增殖因子活化受体γ(PPARγ)信号对大鼠肝星状细胞(HSC)活化、基质金属蛋白酶(MMPs)活性和胞核核因子-κBp65(RelA)表达的影响。方法采用肝脏原位灌流酶消化、Nycodenz密度梯度离心法分离大鼠HSC。药物处理后收集裂解细胞,Western blot检测PPARγ、α平滑肌肌动蛋白(αSMA)、Ⅰ型胶原、RelA。收集细胞培养上清,明胶酶谱法检测MMP2、9的活性。结果随着HSC活化程度增加PPARγ表达水平不断下降,姜黄素上调其表达水平(P<0·01),拮抗剂GW9662显著阻断这种作用(P<0·01)。姜黄素抑制αSMA的表达、I型胶原的生成以及胞核内活化RelA的表达(P<0·01),显著升高MMP2、9的活性(P<0·01)。结论姜黄素激活PPARγ信号途径抑制HSC活化,升高MMP2、9活性,抑制/干扰NFκB的核转位。

英文摘要:

Objective To study the effect of curcumin on the activity of matrix metalloproteinases(MMPs) and nuclear expression of RelA in rat hepatic stellate cells(HSCs) by activating peroxisome proliferator-activated receptor γ(PPARγ) signal in vitro.Methods HSCs were isolated from SD rats through in situ perfusion of liver,digestion with pronase E and density-gradient centrifugation with Nycodenz.The lytic HSCs were collected after treatment to extract the total protein and nucleoprotein for detecting the expression of PPARγ,αSMA,collagen type Ⅰ and RelA by Western blot,and the supernatant was collected to measure the activity of MMP2 and MMP 9 by gelatin zymograph method.Results The PPARγ expression decreased gradually with increasing of HSC activation,which was up-regulated by curcumin(P<0.01);curcumin inhibited the expression of αSMA,the production of collagen type Ⅰ,and the nuclear expression of activated RelA(P<0.01),and elevated the activity of MMP2 and MMP9 significantly(P<0.01).However,these effects were weakened by the PPARγ antagonist,GW9662,significantly(P<0.01).Conclusion By activating PPARγ signal transduction pathway curcumin treatment can inhibit HSC activation,increase the activity of MMP2 and MMP9 and inhibit/interfere nuclear translocation of NFκB.

关闭