天然抗氧化剂丹参酮Ⅱ—A对肝细胞脂质过氧化产物与DNA相互作用的影响  

EFFECT OF NATURAL ANTIOXIDANT TANSHINONE Ⅱ-A ON INTERACTION OF LIPID PEROXIDATION PRODUCTS AND DNA IN LIVER CELLS

作　　者：曹恩华[1] 刘晓麒[1] 李景福[1] 许娜飞[1] 秦静芬[1] 陈天明[1] 王苏生 俞信 

机构地区：[1]中国科学院生物物理研究所,北京理工大学工程光学系

出　　处：《生物物理学报》1996年第2期339-344,共6页Acta Biophysica Sinica

基　　金：国家自然科学基金

摘　　要：［３Ｈ］花生四烯酸标记的肝细胞，经ＦｅＣｌ２－ＤＴＰＡ启动脂质过氧化后，细胞ＤＮＡ出现放射性，并随保温时间增加而逐渐增高，表明在细胞内脂质过氧化产物与ＤＮＡ发生相互作用，生成了一种ＤＮＡ加成物，经测定它具有特征荧光光谱，显示较低的增色效应和Ｔｍ值。用高度敏度荧光图象显微镜直接观察发现丹参酮Ⅱ－Ａ经细胞摄取后主要滞留在细胞膜与胞浆中。它能有效地抑制细胞脂质过氧化，减少脂质－ＤＮＡ加成物的产生，并阻止了细胞存活率和Ｏ６甲基鸟嘌呤转移酶活性的降低，其抑制率与ＶｉｔＥ，ＢＨＴ相近，但显著高于ＮａＮ３，甘露醇和ＳＯＤ。上述结果提示丹参酮Ⅱ－Ａ是一种新的有效的细胞内脂质过氧化产物与ＤＮＡ相互作用的抑制剂。它对ＤＮＡ的保护作用可能是通过清除脂类自由基而阻断脂质过氧化的链式反应，抑制ＤＮＡ加成物的生成，从而减少了细胞毒性。In the present study,effects of Tanshinone Ⅱ-A on the interaction of lipid peroxidation products and DNA investigated by using [3H] arachidonic acid, labeled liver cells in the presence of FeCl2-DTPA.The nuclear DNA isolated from treated cells had higher radioactivity as compared with controls and the radioactivity increased with longer incubation time.Purified lipid-DNA adducts had a characteristic fluorescent spectrum and showed a decrease of hyperchromicity and melting point.TS Ⅱ-A was mainly located in the cell membrane and cytoplasm as shown by ultrasensitive fluorescence microscopic imaging observation.TS Ⅱ-A could inhibit the association of peroxidation products with DNA in liver cells and prevent a decrease in cell viability and activity of O6-methylguanine acceptor plotein with increasing incubation the.Compared with ogher antioxidants, TS Ⅱ-A had a higher inhibitory ratio which was similar to vitamin E and butylated hydroxy-toluene, but markedly stronger than NaN3,mannatol and superoxide dismutase. The results suggest that TS Ⅱ-A represents a new and effective antioxidant that inhibits the association of lipid peroxidation products with DNA.its protective effect may be showed through breaking the chain reactions of peroxidation by scavenging lipid free radicals,leading to a decrease in the formation of DNA adducts, thereby decreasing their cytotoxicity.

关 键 词：肝细胞 过氧化脂质 丹参酮II-A DNA加成物 

分 类 号：R39.27[医药卫生—基础医学]