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

作　　者：成扬[1] 平键[1] 刘成[1] 徐列明[1] 

机构地区：[1]上海中医药大学附属曙光医院肝病研究所,上海201203

出　　处：《中国中西医结合杂志》2007年第5期439-443,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金项目(No.30300458)

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。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 lyric 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 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 

分 类 号：R285.5[医药卫生—中药学]