姜黄素激活PPARγ下调肝星状细胞α-SMA和Ⅰ型胶原的基因表达  

Inhibiting effects of curcumin on gene expression of α smooth muscle actin and collagen Ⅰin rat's hepatic stellate cells by activating PPARγ signal transduction pathway

作　　者：平键[1] 成扬[1] 徐列明[1] 刘成[1] 谭英姿[1] 

机构地区：[1]上海中医药大学附属曙光医院上海中医药大学肝病研究所,上海201203

出　　处：《中国中西医结合消化杂志》2006年第4期215-218,共4页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家自然科学基金项目(30300458)

摘　　要：[目的]研究姜黄素抑制大鼠肝星状细胞（HSC）活化作用与过氧化物酶体增殖因子活化受体γ（PPARγ）信号转导途径之间的关系。[方法]肝脏原位灌流酶消化、Nycodenz密度梯度离心方法分离培养大鼠HSC，并使用姜黄素对细胞进行相应处理，采用四甲基偶氮唑蓝（MTT）比色分析法检测姜黄素对细胞增殖的影响。收集裂解细胞并抽提细胞总RNA，采用半定量RT-PCR检测姜黄素处理对α平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原的基因表达水平的影响。[结果]姜黄素在10-50μmol／L范围内呈剂量依赖性抑制体外培养大鼠传代HSC的增殖，且能在基因水平显著降低α-SMA（P〈0．05）和Ⅰ型胶原的基因表达水平（P〈0．01）。这些作用均可以被PPARγ特异性阻断剂GW9662阻断。[结论]姜黄素抑制HSC增殖、活化和合成Ⅰ型胶原的作用依赖于PPARγ信号转导途径的激活。[Objective] To study the effect of curcumin on the gene expression of α smooth muscle actin （α-SMA） and collagen Ⅰ in subcultured rat＇s hepatic stellate cells （HSCs） by activating peroxisome proliferator-activated receptor γ （PPARγ） signal transduction pathway. [Methods] The HSCs were isolated from SD rats through in situ perfusion of liver with pronase E and density-gradient centrifugation with Nycodenz. The subcultured cells were treated with corresponding compound. The inhibition effect on HSCs proliferation was determined by MTT colorimetry. The effect of curcumin on PPARγ signal transduction pathway was confirmed by its antagonist application. The total RNA was extracted by Trizol reagent and the gene expression level of α-SMA and collagen Ⅰ was determined by semi-quantitative RT-PCR. [Results] The MTT analysis results showed that curcumin inhibited HSCs proliferation between 10and 50 mmol/L in dose-dependent manner. And the semi-quantitative RT-PCR results showed that the gene expression level of α-SMA and collagen Ⅰ was down-regulated significantly after curcumin treatment, while all the effects of curcumin on HSCs could be reversed by PPARγ antagonist GW9662. [Conelusion]The effects of curcumin on inhibiting HSCs cell proliferation, gene expression level of α-SMA and collagen Ⅰ are dependent on activating PPARγ signal transduction pathway.

关 键 词：肝纤维化 姜黄素 肝星状细胞 过氧化物酶体增殖因子活化受体Γ Α平滑肌肌动蛋白 Ⅰ型胶原 

分 类 号：R575[医药卫生—消化系统] R284.1[医药卫生—内科学]