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

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PPAR7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。

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 gamma signal]

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 gamma (PPARgamma) 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 PPARgamma, alphaSMA, 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 PPARgamma expression decreased gradually with increasing of HSC activation, which was up-regulated by curcumin (P < 0.01); curcumin inhibited the expression of aSMA, 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 PPARgamma antagonist, GW9662, significantly (P < 0.01). CONCLUSION: By activating PPARgamma signal transduction pathway curcumin treatment can inhibit HSC activation, increase the activity of MMP2 and MMP9 and inhibit/ interfere nuclear translocation of NFkappaB.