抗癌药物巴豆生物碱、顺铂对红细胞膜的作用

THE EFFECTS OF ANTITUMOR AGENTS OF CROTON ALKALOIDS AND CISPLATIN ON HUMAN RED BLOOD CELL MEMBRANES

作者利用圆二色技术、荧光技术和紫外吸收技术研究了药物对红细胞膜和牛血清清蛋白（ＢＳＡ）的作用。通过测２００～２４０ｎｍ的圆二色谱，发现经巴豆碱作用后，红细胞膜和ＢＳＡ的α螺旋量增加。顺铂对红细胞膜的α螺旋量也有影响。荧光实验得出，加巴豆碱后，ＢＳＡ的荧光发时峰蓝移，强度淬灭，可能反映了表面色氨酸残基内缩到蛋白质的疏水内核。这和加巴豆碱后α螺旋增加一致。荧光极化率的测定，结果表明，巴豆碱使红细胞膜的流动性减小，而顺铂对红细胞膜的流动性没有影响。用紫外技术可检侧到巴豆碱与红细胞膜作用后的动力学过程。本研究结果表明，巴豆碱和顺铂都能使膜蛋白的二级结构发生改变，巴豆碱和顺铂可能是通过改变蛋白质的空间构象而发生药理作用的。

AbstractThe effects of antitumor drugs of croton alkaloids (CA)extractedfrom croton,and cisplatin on the structure of human erythrocyte membrane and bovine serum albumin(BSA)were studied with the techniques of circular dichroism,fluorescence spectroscopy and ultraviolet absorption. Frommeasuring circular dichroism between 200～240nm, it was found that the α helix of membrane andBSA increased after CA addition. Cisplatin was also found effective in altering membrane α helicalcontent. BSA showed a loss of fluorescence intensity and a blue-shift of emission peak after CA ad-dition. The fluorescence quenching and peak shift may reflect the movement of tryptophan to amore nonpolar environment(the hydrophobic portions of proteins).This is consistent with the in-crease in heiicity of BSA in the presence of CA. From measuring fluorescence polarization of mem-brane,it was found that membrane fluidity decreased in the presence of CA, but did not change inthe presence of cisplatin, The results indicate that both CA and cisplatin lead to alterations in the sec-ondary structure of membrane protein. The conformation change in membrane protein may accountfor the pharmocological effect of CA and cisplatin.