血红素氧合酶-1在姜黄素抑制氧化型低密度脂蛋白诱导大鼠血管平滑肌细胞增殖中的作用  

Role of heme oxygenase-1 on curcumin inhibiting rat vascular smooth muscle cells proliferation induced by oxidized low density lipoprotein

作　　者：钟毅[1] 赖文岩[1] 刘挺榕[1] 郭志刚[1] 

机构地区：[1]南方医科大学南方医院心内科,广州510515

出　　处：《重庆医学》2012年第16期1609-1611,F0003,F0004,共5页Chongqing medicine

摘　　要：目的观察姜黄素对氧化型低密度脂蛋白(Ox-LDL)诱导的大鼠血管平滑肌细胞(VSMC)增殖的影响,并探讨血红素氧合酶-1(HO-1)在姜黄素抑制血管平滑肌细胞增殖中的作用及机制。方法体外分离培养大鼠血管平滑肌细胞并行免疫组化鉴定,以四甲基偶氮唑盐(MTT)法测定细胞增殖率、逆转录-聚合酶链式反应(RT-PCR)检测HO-1mRNA水平,蛋白免疫印迹法(Western blot)分别检测HO-1及增殖细胞核抗原(PCNA)蛋白表达水平。结果 Ox-LDL呈浓度依赖性(0～150μg/mL)地诱导VSMC增殖,达到200μg/mL具有细胞毒性;姜黄素呈浓度依赖性(40、80μmol/L)地抑制Ox-LDL(100μg/mL)所诱导的VSMC增殖,HO-1抑制剂锌原卟啉Ⅸ(ZnPPⅨ)可明显减弱此抑制效应;姜黄素可诱导VSMC上调HO-1mRNA和蛋白表达;姜黄素可减弱Ox-LDL诱导VSMCs增殖细胞核抗原的高表达,此效应可被HO-1抑制剂ZnPPⅨ抑制。结论姜黄素通过降低HO-1介导的PCNA表达,进而抑制Ox-LDL诱导大鼠血管平滑肌增殖。Objective To investigate the inhibitory effect of curcumin on oxidized（Ox）-low density lipoprotein（LDL）-induced rat vascular smooth muscle cells proliferation and to explore the role of heme oxygenase-1 in this process. Methods The cultured aortic smooth muscle cells isolated from male Sprague-Dawley rats were verified by immunohistochemistry. The cell viability was assayed by MTT, and reverse transcription-polymerase chain reaction（RT-PCR） was performed to determine the level of HO- lmRNA. In addition, HO-1 and PCNA expression were analyzed by Western blotting. Results The Ox-LDL remarkably stimulated VSMCs proliferation in a concentration-dependent manner（0-150 ~g/ml） ,however, the doses that exceeded 200 mg/ml had a cyto- toxic effect. Curcumin also attenuated the VSMCs proliferation effect of Ox-LDL in a concentration-dependent manner（40, 80μM）, the inhibitory effect was blocked by a HO-1 inhibitor（zine protoporphyrin Ⅸ, ZnPPⅨ ）. Curcumin significantly upregulated HO- l mRNA and protein expression in a concentration-dependent manner. Furthermore,ZnPPⅨ blocked the inhibitory effect of curcu- min on Ox-LDL-induced PCNA expression. Conclusion Curcumin inhibits Ox-LDL-induced rat vascular smooth muscle cells prolif eration via HO-l-mediated down-regulation of PCNA expression.

关 键 词：姜黄素 氧合酶类 脂蛋白类 LDL 

分 类 号：R285.5[医药卫生—中药学]