高三尖杉酯碱治疗急性白血病机制的研究

目的：探讨高三尖杉酯碱(HHar)对AML的疗效明显优于ALL的可能机制。方法：以成人AL原代细胞为研究对象,利用其遗传性和体内细胞相似的特点,模拟人体用药后的最大血药浓度,采用高、中、低3种浓度梯度对HHar进行研究。采用光镜、扫描电镜、透射电镜、DNA凝胶电泳、二苯胺法、流式细胞术等方法,充分证实HHar确可诱导AL原代细胞凋亡。并进一步选取其中较为经济的光镜下计数细胞凋亡率、二苯胺法定量测定凋亡细胞的DNA片段化率及锥虫蓝染色光镜下计数坏死率3种方法定量观察HHar对ALL及AML原代细胞的诱导凋亡和杀伤,得出相应的时间—剂量—效应关系,并进行对比分析。结果：HHar可诱导AL原代细胞凋亡,AML原代细胞对HHar诱导凋亡的敏感性高于ALL原代细胞。结论：AML原代细胞对HHar诱导凋亡的敏感性高于ALL原代细胞,这是其临床疗效优于ALL的可能机制。

The Mechanism of HHar in Treating Acute Leukemia

Objective:To detect the possible mechanism that HHar is more effective in AML than in ALL.Methods:Primary acute leukemia cells of 34 patients (AML 19,ALL 15) were treated with HHar in 3 concentration gradients.First,light microscope,the SEM and TEM,DNA agarose gel electrophoresis,diphemylamine reaction and cytometry were used to prove that HHar could induce primary acute leukemia cells apoptosis.Second,the apoptotic rates and necrosis rates were calculated under the light microscope respectively and the internucleosomal DNA fragmentation ratios with diphemylamine reaction of the primary acute leukemia cells treated with HHar were measured.Finally,the time dose effect relationships were analyzed furthermore.Results:HHar can induce the apoptosis of primary AL cells and the AML primary cells were more sensitive the apoptosis induced by HHar than the ALL ones.Conclusion:The AML primary cells were more sensitive to the apoptosis induced by HHar than the ALL ones.These may be the possible mechanism that HHar is more effective in AML than ALL.