盐酸吉西他滨降解实验研究.doc

盐酸吉西他滨降解实验研究
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of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist7
of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist18

of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist
of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist7
of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist18

of accountability, redress of orders and prohibitions. Strengthening the honesty and self-discipline of leading cadres honesty in politics and education work, enhance leaders ability to resist
一、文献综述
（一）盐酸吉西他滨的化学名和药理作用及药代动力学
盐酸吉西他滨英文名为Gemcitabine Hydrochloride。化学名为：4-氨基-1-(3,3-二氟-4-羟基-5-羟甲基四氢呋喃-2-基)-1H-嘧啶-2-酮盐酸盐。
盐酸吉西他滨作为一种前药在细胞内是脱氧胸苷激酶磷酸化的良好底物，在酶的作用下转化成下列代谢物：吉西他滨一磷酸盐（dFdCMP）、吉西他滨二磷酸盐（dFdCDP）和吉西他滨三磷酸盐（dFdCTP）其中dFdCDP和dFdCTP为活性产物。dFdCDP抑制核糖核苷酸还原酶，从而减少了DNA合成的修复所需的脱氧核苷酸的量（尤其是dCTP），低水平的dCTP逆转了脱氧苷激酶正常的负反馈抑制，导致dFdCTP更多的积聚。同时dFdCDP抑制了dCTP诱导的脱氧胞氨酶对dFdCMP的脱氨作用，且dFdCTP直接抑制脱氧胞苷脱酶，从而使更多的dFdCMP转化成活性代谢物dFdCMP的脱氨作用，且dFdCTP直接抑制脱氧胞苷脱氨酶，从而使更多的dFdCMP转化成活性代谢物dFdCDP，dFd-CTP而dFdCTP则与dCTP竞争结合进入DNA链，插入至DNA链中脱氧胞苷的位点，并允许鸟苷与其配对,盐酸吉西他滨分子就被此鸟苷“掩蔽”使其免受核糖核酸外切酶的移除修复，然后DNA链合成停止，进而DNA断裂、细胞死亡。
盐酸吉西他滨在静注后，很快的分布到全身各组织，输注时间越长，就越广，越深入，半衰期也就越长。在短时间输注下，半衰期约为32min~94min,在结束输注5min内， ~,本品仅有少数与蛋白质结合，能被胞苷脱氨酸在肝脏，肾，血液和其他组织中快速完全的代谢，只